Skip to main content
SpringerLink
Log in

Molecular pathophysiology of voltage-gated ion channels

  • Chapter
  • First Online:
Reviews of Physiology Biochemistry and Pharmacology, Volume 128

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 128))

Abstract

In addition to the clarification of the pathology of a whole group of hereditary diseases, the study of the consequences of these mutations at the levels of the whole system (patient), organ and cells (excised muscle specimens), and of the channel proteins has taught us that our current opinions on channel structure-function relations are far from being comprehensive. For instance it had been assumed that as in the potassium channel, also in the sodium and calcium channel proteins, the S4 unit is mainly responsible for channel activation. This notion has to be corrected as mutations in S4 of repeat IV were found to affect mainly channel inactivation. Moreover mutations affecting other channel domains, such as interlinkers or other intramembraneous subunits cause virtually the same alterations, not only when tested with the limited probe of the patch clamp but also on the level of the patient. The lack of mutations in other parts of the genes, in particular those coding for sodium or calcium channels, may indicate that proper function of the corresponding protein domains is essential for life. Thus the knowledge derived from the experiments of Nature, as these diseases may be looked upon by the cell biologist, provides a valuable addition to the results from site-directed mutagenesis. For a final understanding of the pathology of the diseases, for example, triggering effects of cold or potassium, it seems that the regression from the proteins back to the cellular or even systemic levels is unavoidable.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abdalla JA, Casley WL, Cousin HK, Hudson AJ, Murphy EG, Cornélis FC, Hashimoto L, Ebers GC (1992) Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome 7q35. Am J Hum Genet 51:579–584

    Google Scholar 

  • Adams BA, Beam KG (1989) A novel calcium current in dysgenic skeletal muscle. J Gen Physiol 94:429–444

    Google Scholar 

  • Adkison L, Harris B, Lane PW, Davisson MT (1989) New alleles of “arrested development of righting response (adr).” Mouse News Lett 84:89–90

    Google Scholar 

  • Adrian RH, Bryant SH (1974) On the repetitive discharge in myotonic muscle fibres. J Physiol Paris 240:505–515

    Google Scholar 

  • Adrian RH, Marshall MW (1976) Action potentials reconstructed in normal and myotonic muscle fibres. J Physiol Paris 258:125–143

    Google Scholar 

  • Ahmed CH, Ware DH, Lee SC, Patten CD, Ferrer-Montiel AV, Schinder AF, McPherson JD, Wagner-McPherson CB, Wasmuth JJ, Evans GA, Montal M (1992) Primary structure, chromosomal location, and functional expression of a voltage-gated sodium channel from human brain. Proc Natl Acad Sci USA 89:8220–8224

    Google Scholar 

  • Angaut-Petit D, McArdle JJ, Mallart A, Bournaud R, Pinhon-Raymond M, Rieger F (1982) Electrophysiological and morphological studies of a motor nerve in “motor endplate disease” of the mouse. Proc R Soc Lond B Biol Sci 215:117–125

    Google Scholar 

  • Armstrong CM, Bezanilla F (1977) Inactivation of the sodium channel: II. Gating current experiments. J Gen Physiol 70:567–590

    Google Scholar 

  • Armstrong CM, Bezanilla F, Rojas E (1973) Destruction of sodium conductance inactivation in squid axons perfused with pronase. J Gen Physiol 62:375–391

    Google Scholar 

  • Backx PH, Yue DT, Lawrence JH, Marban E, Tomaselli GF (1992) Molecular localization of an ion-binding site within the pore of mammalian sodium channels. Science 257:248–51

    Google Scholar 

  • Baquero JL, Ayala RA, Wang J, Curless RG, Feero WG, Hoffman EP, Ebeid MR (1995) Hyperkalemic periodic paralysis with cardiac dysrhythmia: a novel sodium channel mutation? Ann Neurol 37:408–411

    Google Scholar 

  • Barchi RL (1995) Molecular pathology of the skeletal muscle sodium channel. Annu Rev Physiol 57:355–385

    Google Scholar 

  • Bardouille C, Vullhorst D, Jockusch H (1996) Chloride channel 1 mRNA as a marker of myotube maturation. J Cell Sci (in preparation)

    Google Scholar 

  • Beam KG, Knudson CM (1988a) Calcium currents in embryonic and neonatal mammalian skeletal muscle. J Gen Physiol 91:781–798

    Google Scholar 

  • Beam KG, Knudson CM (1988b) Effect of postnatal development on calcium currents and slow charge movement in mammalian skeletal muscle. J Gen Physiol 91:799–815

    Google Scholar 

  • Beam KG, Knudson CM, Powell JA (1986) A lethal mutation in mice eliminates the slow calcium current in skeletal muscle cells. Nature 320:168–170

    Google Scholar 

  • Beam KG, Brett AA, Niidome T, Numa S, Tanabe T (1992) Function of a truncated dihydropyridine receptor as both voltage sensor and calcium channel. Nature 360:169–171

    Google Scholar 

  • Beck C, Fahlke C, George AL (1996) Altered voltage-dependent activation of skeletal muscle Cl-channel causes myotonia in the fainting goat. Biophys J 70:A69

    Google Scholar 

  • Becker PE (1957) Zur Frage der Heterogenie der erblichen Myotonien. Nervenarzt 28:455–460

    Google Scholar 

  • Becker PE (1970) Paramyotonia congenita (Eulenburg). Fortschritte der allgemeinen und klinischen Humangenetik. Thieme, Stuttgart

    Google Scholar 

  • Becker PE (1977) Myotonia congenita and syndromes associated with myotonia. Thieme, Stuttgart

    Google Scholar 

  • Bennett PB, Yazawa K, Makita N, George AL Jr (1995) Molecular mechanism for an inherited cardiac arrhythmia. Nature 376:683–685

    Google Scholar 

  • Bezanilla F, Armstrong CM (1977) Inactivation of the sodium channel I. Sodium current experiments. J Gen Physiol 70:549–566

    Google Scholar 

  • Blaxter AC, Lievesley P, Gruffydd-Jones T, Wotton P (1986) Periodic muscle weakness in burmese kittens. Vet Rec (May 31) pp 619–620

    Google Scholar 

  • Block BA, Imagawa T, Campbell KP, Franzini-Armstrong C (1988) Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle. J Cell Biol 107:2587–2600

    Google Scholar 

  • Bosse E, Regulla S, Biel M, Ruth P, Meyer HE, Flockerzi V, Hofmann F (1990) The cDNA and deduced amino acid sequence of the gamma subunit of the L-type calcium channel from rabbit skeletal muscle. FEBS Lett 267:153–156

    Google Scholar 

  • Bradley W, Taylor R, Rice D, Hausmanowa-Petruzewicz I, Adelman L, Jenkison M, Jedrzejowska H, Drac H, Pendlebury W (1989) Progressive myopathy in hyperkalemic periodic paralysis. Arch Neurol 47:1013–1017

    Google Scholar 

  • Bretag AH (1987) Muscle chloride channels. Physiol Rev 67:618–725

    Google Scholar 

  • Browne DL, Gancher ST, Nutt JG, Brunt ERP, Smith EA, Kramer P, Litt M (1994) Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet 8:136–140

    Google Scholar 

  • Browne DL, Brunt ERP, Griggs RC, Nutt JG, Gancher ST, Smith EA, Litt M (1995) Identification of two new KCNA1 mutations in episodic ataxia/myokymia families. Hum Mol Genet 4:1671–1672

    Google Scholar 

  • Brunt ERP, van Weerden TW (1990) Familial paroxysmal kinesigenic ataxia and continuous myokymia. Brain 113:1361–1382

    Google Scholar 

  • Bryant SH (1969) Cable properties of external intercostal muscle fibres from myotonic and non-myotonic goats. J Physiol Paris 204:539–550

    Google Scholar 

  • Bryant SH (1973) The electrophysiology of myotonia with a review of congenital myotonia of goats. In: Desmedt JE (ed) New developments in electromyography and clinical neurophysiology, vol 1. Karger, Basel, pp 407–412

    Google Scholar 

  • Bryant SH (1976) Altered membrane properties in myotonia. In: Bolis L, Hoffman LP, Leaf A (eds) Membranes and diseases. Raven, New York, pp 197–206

    Google Scholar 

  • Bryant SH (1982) Physical basis of myotonia. In: Schotland DL (ed) Disorders of the motor unit. Wiley, New York, pp 381–389

    Google Scholar 

  • Bryant SH, Morales-Aguilera A (1971) Chloride conductance in normal and myotonic muscle fibres and the action of monocarboxylic aromatic acids. J Physiol (Paris) 219:361–383

    Google Scholar 

  • Bryant SH, Mambrini M, Entrikin RK (1987) Chloride and potassium membrane conductances are decreased in skeletal muscle fibers from the (mto) myotonic mouse. Neuroscience 465:17

    Google Scholar 

  • Burgess DL, Kohrman DC, Galt J, Plummer NW, Jones JM, Spear B, Meisler MH (1995) Mutation of a new sodium channel gene, Scn8a, in the mouse mutant “motor end-plate disease”. Nat Genet 10:461–465

    Google Scholar 

  • Burton F, Dörstelmann U, Hunter OF (1988) Single-channel activity in sarcolemmal vesicles from human and other mammalian muscles. Muscle Nerve 11:1029–1038

    Google Scholar 

  • Cannon SC, Corey DP (1993) Loss of Na+ channel inactivation by anemone toxin (ATXII) mimics the myotonic state in hyperkalemic periodic paralysis. J Physiol (Lond) 466:501–520

    Google Scholar 

  • Cannon SC, Strittmatter SM (1993) Functional expression of sodium channel mutations identified in families with periodic paralysis. Neuron 10:317–326

    Google Scholar 

  • Cannon SC, Brown RH Jr, Corey DP (1991) A sodium channel defect in hyperkalemic periodic paralysis: potassium-induced failure of inactivation. Neuron 6:619–626

    Google Scholar 

  • Cannon SC, Brown RH Jr, Corey DP (1993a) Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels. Biophys J 65:270–288

    Google Scholar 

  • Cannon SC, McClatchey AI, Gusella JF (1993b) Modification of the Na+ current conducted by the rat skeletal muscle α subunit by coexpression with a human brain β subunit. Pflügers Arch 423:155–157

    Google Scholar 

  • Castellano A, Wei X, Birnbaumer L, Perez-Reyes E (1993) Cloning and expression of a neuronal calcium channel β subunit. J Biol Chem 268:12359–66

    Google Scholar 

  • Catterall WA (1991) Functional subunit structure of voltage-gated calcium channels. Science 253:1499–1500

    Google Scholar 

  • Catterall WA (1992) Cellular and molecular biology of voltage-gated sodium channels. Physiol Rev 72:S15–S48

    Google Scholar 

  • Catterall WA, Striessnig J (1992) Receptor sites for Ca2+ channel antagonists. Trends Pharmacol Sci 13:256–262

    Google Scholar 

  • Chahine M, George AL, Zhou M, Ji S, Sun W, Barchi RL, Horn R (1994) Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation. Neuron 12:281–294

    Google Scholar 

  • Chandy KG, Gutman GA (1995) Voltage-gated K+ channel genes. In: North RA (ed) Handbook of receptors and channels: ligand-and voltage-gated ion channels. CRC Press, Boca Raton, pp 1–71

    Google Scholar 

  • Chaudhari N (1992) A single nucleotide deletion in the skeletal muscle-specific calcium channel transcript of muscular dysgenesis (mdg) mice. J Biol Chem 267:25636–25639

    Google Scholar 

  • Chen C, Cannon SC (1995) Modulation of Na+ channel inactivation by the β1 subunit: a deletion analysis. Pflügers Arch 431:186–195

    Google Scholar 

  • Chen L-Q, Chahine M, Kallen RG, Barchi RL, Horn R (1992) Chimeric study of sodium channels from rat skeletal and cardiac muscle. FEBS Lett 309:253–57

    Google Scholar 

  • Chen M, Niggeweg R, Jockusch H (1996) Chloride conductance in mutant mouse muscle is subject to functional gene dosage compensation. J Physiol (Lond) (submitted)

    Google Scholar 

  • Chin H, Kozak CA, Kim H-L, Mock B, McBride OW (1991) A brain L-type calcium channel α1 subunit gene (CCHL1A2) maps to mouse chromosome 14 and human chromosome 3. Genomics 11:914–919

    Google Scholar 

  • Chua M, Betz WJ (1991) Characterisation of ion channels on the surface membrane of adult rat skeletal muscle. Biophys J 59:1251–1260

    Google Scholar 

  • Clark SL, Luton FH, Cutler JT (1939) A form of congenital myotonia in goats. J Nerv Ment Dis 90:297–309

    Google Scholar 

  • Clausen T, Kohn PG (1977) The effect of insulin on the transport of sodium and potassium in rat soleus muscle. J Physiol Paris 265:19–42

    Google Scholar 

  • Cognard C, Lazdunski M, Romey G (1986) Different types of Ca2+ channels in mammalian skeletal muscle cells in culture. Proc Natl Acad Sci USA 83:517–521

    Google Scholar 

  • Cognard C, Constantin B, Rivet M, Imbert N, Besse C, Raymond G (1992) Excitation-contraction coupling in rat skeletal muscle cells: evolution during in vitro myogenesis. In: Frank GB (ed) Excitation-contraction coupling in skeletal, cardiac and smooth muscle. Plenum, New York, pp 73–89

    Google Scholar 

  • Cognard C, Constantin B, Rivet-Bastide M, Raymond G (1993a) Intracellular calcium transients induced by different kinds of stimulus during myogenesis of rat skeletal muscle cells studied by laser cytofluorimetry with Indo-1. Cell Calcium 14:333–348

    Google Scholar 

  • Cognard C, Lazdunski M, Romey G (1993b) Appearance and evolution of calcium currents and contraction during the early post-fusional stages of rat skeletal muscle cells developing in primary culture. Development 117:1153–1161

    Google Scholar 

  • Cooper DN, Krawczak M (1990) The mutational spectrum of single base-pair substitutions causing human genetic disease; patterns and predictions. Hum Genet 85:55–74

    Google Scholar 

  • Cota G, Stefani E (1986) A fast activated inward calcium current in twitch muscle fibres of the frog (Rana montezume). J Physiol (Lond) 370:151–163

    Google Scholar 

  • Cox JH (1985) An episodic weakness in four horses associated with intermittent serum hyperkalemia and the similarity of the disease to hyperkalemic periodic paralysis in man. Proc Am Ass Equine Practice 31:383–390

    Google Scholar 

  • Cummins TR, Zhou J, Sigworth FJ, Ukomadu C, Stephan M, Ptáček LJ, Agnew WS (1993) Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis. Neuron 10:667–678

    Google Scholar 

  • Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80:795–803

    Google Scholar 

  • Davisson MT, Harris B, Lane PW (1989) Mouse News Lett 83:167

    Google Scholar 

  • DeCoursey TE, Bryant SH, Owenburg KM (1981) Dependence of membrane potential on extracellular ionic concentrations in myotonic goats and rats. Am J Physiol 240:C56–C63

    Google Scholar 

  • DeJong JGY (1966) Myotonia levior. In: Kuhn E (ed) Progressive Muskeldystrophie — Myotonie — Myasthenie. Springer Verlag, Berlin Heidelberg New York, pp 255–259

    Google Scholar 

  • DeJongh KS, Warner C, Colvin AA, Catterall WA (1991) Characterization of the two size forms of the α1 subunit of skeletal muscle L-type calcium channels. Proc Natl Acad Sci USA 88:10778–82

    Google Scholar 

  • Denborough MA, Lovell RRH (1960) Anaesthetic deaths in a family. Lancet 2:45

    Google Scholar 

  • DeSilva SM, Kuncl RW, Griffin JW, Cornblath DR, Chavoustie S (1990) Paramyotonia congenita or hyperkalemic periodic paralysis? Clinical and electrophysiological features of each entity in one family. Muscle Nerve 13:21–26

    Google Scholar 

  • Deufel T, Golla A, Iles D, Meindl A, Meitinger T, Schindelhauer D, DeVries A, Pongratz D, MacLennan D, Johnson KJ, Lehmann-Horn F (1992) Evidence for genetic heterogeneity of malignant hyperthermia susceptibility. Am J Hum Genet 50:1151–1161

    Google Scholar 

  • Disteche CM (1995) Escape from X inactivation in human and mouse. Trends Genet 11:17–22

    Google Scholar 

  • Drouet B, Garcia L, Simon-Chazottes D, Mattei MG, Guénet J-L, Schwartz A, Varadi G, Pinçon-Raymond M (1993) The gene encoding for the α1 subunit of the skeletal dihydropyridine receptor (Cchlla3=mdg) maps to mouse chromosome 1 and human 1q32. Mamm Genome 4:499–503

    Google Scholar 

  • Duchen LW (1970) Hereditary motor end-plate disease in the mouse: light and electron microscopic studies. J Neurol Neurosurg Psychiatry 33:238–250

    Google Scholar 

  • Duncan BK, Miller JH (1980) Mutagenic deamination of cytosin residues in DNA. Nature 287:560–561

    Google Scholar 

  • Durell SR, Guy HR (1992) Atomic scale structure and functional models of voltagegated potassium channels. Biophys J 62:238–247

    Google Scholar 

  • Ebers GC, George AL, Barchi RL, Ting-Passador MS, Kallen RG, Lathrop GM, Beckmann JS, Hahn AF, Brown WF, Campbell RD, Hudson AJ (1991) Paramyotonia congenita and hyperkalemic periodic paralysis are linked to the adult muscle sodium channel gene. Ann Neurol 30:810–816

    Google Scholar 

  • Elbaz A, Vale-Santos J, Jurkat-Rott K, Lapie P, Ophoff RA, Bady B, Links TP, Puissan C, Villa A, Monnier N, Padberg GW, Abe K, Feingold N, Guimaraes J, Wintzen AR, Van der Hoeven JH, Saudubray JM, Grundfeld JP, Lenoir G, Nivet H, Echenne B, Frants RR, Fardeu M, Lehmann-Horn F, Fontaine B (1995) Hypokalemic periodic paralysis (hypoPP) and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 Caucasian families. Am J Hum Genet 56:374–380

    Google Scholar 

  • Ellis SB, Williams ME, Ways NR, Brenner R, Sharp AH, Leung AT, Campbell KP, McKenna E, Koch WJ, Hui A, Schwartz A, Harpold MM (1988) Sequence and expression of mRNAs encoding the α1 and α2 subunits of a DHP-sensitive calcium channel. Science 241:1661–64

    Google Scholar 

  • Engel AG, Lambert EH, Rosevaer JW, Newlon TW (1965) Clinical and electromyographic studies in a patient with primary hypokalemic periodic paralysis. Am J Med 38:626–640

    Google Scholar 

  • Entrikin RK, Abresch RT, Larson DB, Levine NA, Sharman RB (1987) Neuromuscular disorders: myotonia and muscular dystrophy in mice. Soc Neurosci Abstr 10:785

    Google Scholar 

  • Erdmann R, Lüttgau HC (1989) The effect of the phenylalkylamine D888 (Devapamil) on force and Ca2+ current in isolated frog skeletal muscle fibres. J Physiol (Lond) 413:521–541

    Google Scholar 

  • Eulenburg A (1886) Über eine familiäre durch 6 Generationen verfolgbare Form congenitaler Paramyotonie. Neurol Zentralbl 5:265–272

    Google Scholar 

  • Fahlke C, Rüdel R (1995) Chloride currents across the membrane of mammalian skeletal muscle fibres. J Physiol (Lond) 484:355–368

    Google Scholar 

  • Fahlke C, Zachar E, Rüdel R (1992) Single-channel recordings of chloride currents in cultured human skeletal muscle. Pflügers Arch 421:108–116

    Google Scholar 

  • Fahlke C, Rüdel R, Mitrovic N, Zhou M, George AL Jr (1995) An aspartic acid residue important for voltage-dependent gating of human muscle chloride channels. Neuron 15:1–20

    Google Scholar 

  • Fahlke C, Rosenbohm A, Mitrovic N, George AL, Rüdel R (1996) Mechanism of voltage-dependent gating in skeletal muscle chloride channels. Biophys J 70:August issue

    Google Scholar 

  • Feero WG, Wang J, Barany F, Zhou J, Todorovic SM, Conwit R, Galloway G, Hausmanowa-Petrusewicz I, Fidzianska A, Arahata K, Wessel HB, Wadelius C, Marks HG, Hartlage P, Hayakawa H, Hoffman EP (1993) Hyperkalemic periodic paralysis: rapid molecular diagnosis and relationship of genotype to phenotype in 12 families. Neurology 43:668–673

    Google Scholar 

  • Flatman JA, Clausen T (1979) Combined effects of adrenaline and insulin on active electrogenic Na+-K+ transport in rat soleus muscle. Nature 281:580–581

    Google Scholar 

  • Fontaine B, Khurana TS, Hoffman EP, Bruns GAP, Haines JL, Trofatter J, Hanson MP, Rich J, McFarlane H, McKenna-Yasek D, Romano D, Gusella JF, Brown RH Jr (1990) Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene. Science 250:1000–1003

    Google Scholar 

  • Fontaine B, Vale Santos JM, Jurkat-Rott K, Reboul J, Plassart E, Rime CS, Elbaz A, Heine R, Guimaraes J, Weissenbach J, Baumann N, Fardeau M, Lehmann-Horn F (1994) Mapping of hypokalemic periodic paralysis (HypoPP) to chromosome 1q31-q32 by a genome-wide search in three European families. Nat Genet 6:267–272

    Google Scholar 

  • Francini-Armstrong C (1970) Studies on the triad. I. Structure of the junction in frog twitch fibers. J Cell Biol 47:488–499

    Google Scholar 

  • Francini-Armstrong C, Jorgensen AO (1994) Structure and development of E-C coupling units in skeletal muscle. Annu Rev Physiol 56:509–534

    Google Scholar 

  • Franke C, Iaizzo PA, Hatt H, Spittelmeister W, Ricker K, Lehmann-Horn F (1991) Altered Na channel activity and reduced Cl conductance cause hyperexcitability in recessive generalized myotonia (Becker). Muscle Nerve 14:762–770

    Google Scholar 

  • Füchtbauer E-M, Reininghaus J, Jockusch H (1988) Developmental control of the excitability of muscle: transplantation experiments on a myotonic mutant. Proc Natl Acad Sci USA 85:3880–3884

    Google Scholar 

  • Gamstorp I (1956) Adynamia episodica hereditaria. Acta Paediatr (Uppsala) Suppl 45:1–126

    Google Scholar 

  • Gancher ST, Nutt JG (1986) Autosomal dominant episodic ataxia: a heterogeneous syndrome. Mov Disord 1:239–253

    Google Scholar 

  • Gautron S, Dos Santos G, Pinto-Henrique D, Koulakoff A, Gros F, Bergwald-Netter Y (1992) The glial voltage-gated sodium channel: cell-and tissue-specific mRNA expression. Proc Natl Acad Sci USA 89:7272–7276

    Google Scholar 

  • Gellens ME, George AL Jr, Chen L, Chahine M, Horn R, Barchi RL, Kallen RG (1992) Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc Natl Acad Sci USA 89:554–558

    Google Scholar 

  • George AL Jr, Knittle T, Tamkun MM (1992a) Molecular cloning of an atypical voltage-gated sodium channel expressed in human heart and uterus: evidence for a distinct gene family. Proc Natl Acad Sci USA 89:4893–4897

    Google Scholar 

  • George AL Jr, Komisarof J, Kallen RG, Barchi RL (1992b) Primary structure of the adult human skeletal muscle voltage-dependent sodium channel. Ann Neurol 31:131–137

    Google Scholar 

  • George AL Jr, Crackover MA, Abdalla JA, Hudson JA, Ebers GC (1993a) Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita). Nat Genet 3:305–310

    Google Scholar 

  • George AL Jr, Iyer GS, Kleinfeld R, Kallen RG, Barchi RL (1993b) Genomic organization of the human skeletal muscle sodium channel gene. Genomics 15:598–606

    Google Scholar 

  • George AL Jr, Knops JF, Han J, Finley WH, Knittle TJ, Tamkun MM, Brown GB (1994a) Assignment of a human voltage-dependent sodium channel α-subunit gene (SCN6A) to 2q21q23. Genomics 19:395–397

    Google Scholar 

  • George AL Jr, Sloan-Brown K, Fenichel GM, Mitchell GA, Spiegel R, Pascuzzi RM (1994b) Nonsense and missense mutations of the muscle chloride channel gene in patients with myotonia congenita. Hum Mol Genet 3:2071–2072

    Google Scholar 

  • George AL Jr, Varkony TA, Drabkin HA, Han J, Knops JF, Finley WH, Brown GB, Ward DC, Haas M (1995) Assignment of the human heart tetrodotoxin-resistant voltagegated Na+ channel α-subunit gene (SCN5A) to band 3p21. Cytogenet Cell Genet 68:67–70

    Google Scholar 

  • Gillard EF, Otsu K, Fujii J, Khanna VK, DeLeon S, Derdemezi J, Britt BA, Duff CL, Worton RG, MacLennan DH (1991) A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia. Genomics 11:751–755

    Google Scholar 

  • Gonoi T, Hasegawa S (1988) Post-natal disappearance of transient calcium channels in mouse skeletal muscle: effects of denervation and culture. J Physiol (Lond) 401:617–637

    Google Scholar 

  • Grafe P, Quasthoff S, Strupp M, Lehmann-Horn F (1990) Enhancement of K+ conductance improves in vitro the contraction force of skeletal muscle in hypokalemic periodic paralysis. Muscle Nerve 13:451–457

    Google Scholar 

  • Gregg RG, Couch F, Hogan K, Powers PA (1993) Assignment of the human gene for the α1-subunit of the skeletal muscle DHP-sensitive calcium channel (CACNL1A3) to chromosome 1q31-32. Genomics 15:107–112

    Google Scholar 

  • Grissmer S, Dethlefs B, Wasmuth JJ, Goldin AL, Gutman GA, Cahalan MD, Chandy KG (1990) Expression and chromosomal localization of a lymphocyte K+ channel gene. Proc Natl Acad Sci USA 87:9411–9416

    Google Scholar 

  • Grob D, Johns RJ, Liljestrand A (1957) Potassium movement in patients with familial periodic paralysis. Am J Med 23:356–375

    Google Scholar 

  • Gronemeier M, Condie A, Prosser J, Steinmeyer K, Jentsch TJ, Jockusch H (1994) Nonsense and missense mutations in the muscular chloride channel gene Clc-1 of myotonic mice. J Biol Chem 269:5963–5967

    Google Scholar 

  • Grosson CLS, Esteban J, McKenna-Yasek D, Gusella JF, Brown RH Jr (1996) Hypokalemic periodic paralysis mutations: confirmation of mutation and analysis of founder effect. Neuromuscul Disord 6:27–31

    Google Scholar 

  • Gründer S, Thiemann A, Pusch M, Jentsch TJ (1992) Regions involved in the opening of ClC-2 chloride channel by voltage and cell volume. Nature 360:759–763

    Google Scholar 

  • Gurnett CA, Kahl SD, Anderson RD, Campbell KP (1995) Absence of the skeletal muscle sarcolemma chloride channel ClC-1 in myotonic mice. J Biol Chem 270:9035–9038

    Google Scholar 

  • Gutman GA, Chandy KG (1993) Nomenclature of mammalian voltage-dependent potassium channel genes. Neuroscience 5:101–106

    Google Scholar 

  • Hartshorne RP, Messner DJ, Coppersmith JC, Catterall WA (1982) The saxitoxin receptor of the sodium channel from rat brain. Evidence for two nonidentical beta subunits. J Biol Chem 257:13888–13891

    Google Scholar 

  • Heine R (1995) Korrelationen von Genotyp und Phänotyp bei Natrium-und Chloridkanalkrankheiten. Dissertation, University of Ulm

    Google Scholar 

  • Heine R, Pika U, Lehmann-Horn F (1993) A novel SCN4A mutation causing myotonia aggravated by cold and potassium. Hum Mol Genet 2:1349–1353

    Google Scholar 

  • Heine R, George AL, Pika U, Deymeer F, Rüdel R, Lehmann-Horn F (1994) Proof of a non-functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion. Hum Mol Genet 3:1123–1128

    Google Scholar 

  • Heine R, Herzog J, Deymeer F, Michaels J, Moog U, Lehmann-Horn F (1996) Genotype-phenotype relations in paramyotonia congenita. Am J Hum Genet (submitted)

    Google Scholar 

  • Heinemann SH, Terlau H, Stühmer W, Imoto K, Numa S (1992) Calcium channel characteristics conferred on the sodium channel by single mutations. Nature 356:441–443

    Google Scholar 

  • Heller AH, Eicher EM, Hallett M, Sidman RL (1982) Myotonia, a new inherited muscle disease in mice. J Neurosci 2:924–933

    Google Scholar 

  • Hirning LD, Fox AP, McCleskey EW, Olivera BM, Thayer SA, Miller RJ, Tsien RW (1988) Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science 239:57–61

    Google Scholar 

  • Hoffman EP, Lehmann-Horn F, Rüdel R (1995) Overexcited or inactive: ion channels in muscle disease. Cell 80:681–686

    Google Scholar 

  • Hofmann F, Biel M, Flockerzi V (1994) Molecular basis for Ca2+ channel diversity. Annu Rev Neurosci 17:399–418

    Google Scholar 

  • Hogan K, Powers PA, Gregg RG (1994) Cloning of the human skeletal muscle α1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3). Genomics 24:608–609

    Google Scholar 

  • Hoshi T, Zagotta WN, Aldrich RW (1990) Biophysical and molecular mechanisms of Shaker potassium channel inactivation. Science 250:533–538

    Google Scholar 

  • Hudson AJ, Ebers GC, Bulman DE (1995) The skeletal muscle sodium and chloride channel disease. Brain 118:547–563

    Google Scholar 

  • Hullin R, Singer-Lahat D, Freichel M, Biel M, Dascal N, Hofmann F, Flockerzi V (1992) Calcium channel β subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain. EMBO J 11:885–90

    Google Scholar 

  • Iaizzo PA, Lehmann-Horn F (1995) Anesthetic complications in muscle disorders. Anesthesiology 82:1093–1096

    Google Scholar 

  • Iaizzo PA, Franke C, Hatt H, Spittelmeister W, Ricker K, Rüdel R, Lehmann-Horn F (1991) Altered sodium channel behaviour causes myotonia in dominantly inherited myotonia congenita. Neuromuscul Disord 1:47–53

    Google Scholar 

  • Iles DE, Segers B, Sengers RCA, Monsieurs K, Heytens L, Halsall PJ, Hopkins PM, Ellis FR, Hall-Curran JL, Stewart AD, Wieringa B (1993a) Genetic mapping of the β1-and γ-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as candidate genes for malignant hyperthermia susceptibility. Hum Mol Genet 2:863–868

    Google Scholar 

  • Iles DE, Segers B, Weghuis DO, Suikerbuijk R, Wieringa B (1993b) Localization of the γ-subunit of the skeletal muscle L-type voltage-dependent calcium channel gene (CACNLG) to human chromosome band 17q24 by in situ hybridization and identification of a polymorphic repetitive DNA sequence at the gene locus. Cytogenet Cell Genet 64:227–230

    Google Scholar 

  • Iles D, Lehmann-Horn F, Deufel T, Scherer SW, Tsui L-C, Olde Weghuis D, Suijkerbuijk RF, Heytens L, Mikala G, Schwartz A, Ellis FR, Stewart AD, Wieringa B (1994) Localization of the gene encoding the α2/δ-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and segregation of flanking markers in malignant hyperthermia susceptible families. Hum Mol Genet 3:969–975

    Google Scholar 

  • Isom LL, DeJongh KS, Patton DE, Reber RFX, Offord J, Charbonneau H, Walsh K, Goldin AL, Catterall WA (1992) Primary structure and functional expression of the β1 subunit of the rat brain sodium channel. Science 256:839–842

    Google Scholar 

  • Isom LL, DeJongh KS, Catterall WA (1994) Auxiliary subunits of voltage-gated ion channels. Neuron 12:1183–1194

    Google Scholar 

  • Isom LL, Ragsdale DS, DeJongh KS, Westenbroek RE, Reber BFX, Scheuer T, Catterall A (1995a) Structure and function of the β2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell 83:443–442

    Google Scholar 

  • Isom LL, Scheuer T, Brownstein AB, Ragsdale DS, Murphy BJ, Catterall WA (1995b) Functional co-expression of the β1 and type IIA α subunits of sodium channels in a mammalian cell line. J Biol Chem 270:3306–3312

    Google Scholar 

  • Jay SD, Ellis SB, McCue AF, Williams ME, Vedvick TS, Harpold MM, Campbell KP (1990) Primary structure of the gamma-subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 248:490–492

    Google Scholar 

  • Jay SD, Sharp AH, Kahl SD, Vedvick TS, Harpold MM, Campbell KP (1991) Structural characterization of the dihydropyridine-sensitive calcium channel α2 subunit and the associated δ peptides. J Biol Chem 266:3287–93

    Google Scholar 

  • Jentsch TJ, Steinmeyer K, Schwarz G (1990) Primary structure of Torpedo marmorata chloride channel isolated by expression cloning in Xenopus oocytes. Nature 348:510–514

    Google Scholar 

  • Jentsch TJ, Günther W, Pusch M, Schwappach B (1995) Properties of voltage-gated chloride channels of the ClC gene family. J Physiol (Lond) 482.P:19S–25S

    Google Scholar 

  • Ji S, Sun W, George AL Jr, Horn R, Barchi RL (1994) Voltage-dependent regulation of modal gating in the rat SkM1 expressed in Xenopus oocytes. J Gen Physiol 104:625–643

    Google Scholar 

  • Jiang C, Atkinson D, Towbin JA, Splawski I, Lehmann MH, Li H, Timothy K, Taggart RT, Schwartz PJ, Vincent GM, Moss AJ, Keating MT (1994) Two long QT syndrome loci map to chromosomes 3 and 7 with evidence for further heterogeneity. Nat Genet 8:141–147

    Google Scholar 

  • Jockusch H (1990) Molecular aspects of myotonia: the ADR mouse as a model. J Neurol Sci (Suppl) 88:9

    Google Scholar 

  • Jockusch H, Bertram K (1986) “Arrested development of righting response” (adr) and “myotonia” (mto) are allelic. Mouse News Lett 75:19–20

    Google Scholar 

  • Jockusch H, Bertram K, Schenk S (1988) The genes for two neuromuscular diseases of the mouse, “arrested development of righting response,” adr, and “myotonia,” mto, are allelic. Genet Res 52:203–205

    Google Scholar 

  • Ju YK, Saint DA, Gage PW (1994) Inactivation-resistant channels underlying the persistent sodium current in rat ventricular myocytes. Proc R Soc Lond B Biol Sci 256:163–168

    Google Scholar 

  • Jurkat-Rott K, Lehmann-Horn F, Elbaz A, Heine R, Gregg RG, Hogan K, Powers P, Lapie P, Vale-Santos JE, Weissenbach J, Fontaine B (1994) A calcium channel mutation causing hypokalemic periodic paralysis. Hum Mol Genet 3:1415–1419

    Google Scholar 

  • Kawasaki M, Uchida S, Monkawa T, Miyawaki A, Mikoshiba K, Marumo F, Sasaki S (1994) Cloning and expression of a protein kinase C-regulated chloride channel abundantly expressed in rat brain neuronal cells. Neuron 12:597–604

    Google Scholar 

  • Kawasaki M, Suzuki M, Uchida S, Sasaki S, Marumo F (1995) Stable and functional expression of the ClC-3 chloride channel in somatic cell lines. Neuron 14:1285–1291

    Google Scholar 

  • Keynes RD (1994) The kinetics of voltage-gated ion channels. Q Rev Biophys 27:339–434

    Google Scholar 

  • Kieferle S, Bens M, Vandewalle A, Jentsch T (1994) Two highly homologous members of the ClC chloride channel family in both rat and human kidney. Proc Natl Acad Sci USA 91:6943–6947

    Google Scholar 

  • Klocke R, Steinmeyer K, Jentsch TJ, Jockusch H (1994) Role of innervation, excitability, and myogenic factors in the expression of the muscular chloride channel ClC-1. J Biol Chem 269:27635–27639

    Google Scholar 

  • Knudson CM, Chaudhari N, Sharp AH, Powell JA, Beam KG, Campbell KP (1989) Specific absence of the α1 subunit of the dihydropyridine receptor in mice with muscular dysgenesis. J Biol Chem 264:1345–1348

    Google Scholar 

  • Koch MC, Ricker K, Otto M, Grimm T, Bender K, Zoll B, Harper PS, Lehmann-Horn F, Rüdel R, Hoffman E (1991) Linkage data suggesting allelic heterogeneity for paramyotonia congenita and hyperkalemic periodic paralysis on chromosome 17. Hum Genet 88:71–74

    Google Scholar 

  • Koch MC, Steinmeyer K, Lorenz C, Ricker K, Wolf F, Otto M, Zoll B, Lehmann-Horn F, Grzeschik KH, Jentsch TJ (1992) The skeletal muscle chloride channel in dominant and recessive human myotonia. Science 257:797–800

    Google Scholar 

  • Koch MC, Baumbach K, George AL, Ricker K (1995) Paramyotonia congenita without paralysis on exposure to cold: a novel mutation in the SCN4A gene (Val1293Ile). Neuroreport 6:2001–2004

    Google Scholar 

  • Költgen D, Reininghaus J, Jockusch H (1989) More evidence against the involvement of neuromuscular transmission in mouse myotonia. Mouse News Lett 83:151

    Google Scholar 

  • Költgen D, Brinkmeier H, Jockusch H (1991) Myotonia and neuromuscular transmission in the mouse. Muscle Nerve 14:775–780

    Google Scholar 

  • Krafte DS, Snutch TP, Leonard JP, Davidson N, Lester HA (1988) Evidence for the involvement of more than one mRNA in controlling the inactivation process of rat and rabbit brain Na channels expressed in Xenopus oocytes. J Neurosci 8:2859–2868

    Google Scholar 

  • Krafte DS, Goldin AL, Auld VJ, Dunn RJ, Davidson N, Lester HA (1990) Inactivation of cloned Na channels expressed in xenopus oocytes. J Gen Physiol 96:689–706

    Google Scholar 

  • Kraner SD, Tanaka JC, Barchi RL (1985) Purification and functional reconstitution of the voltage-sensitive sodium channel from rabbit T-tubular membranes. J Biol Chem 260:6341–47

    Google Scholar 

  • Kwiecinski H (1981) Myotonia induced by chemical agents. Crit Rev Toxicol 8:279–310

    Google Scholar 

  • Kwiecinski H, Lehmann-Horn F, Rüdel R (1984) Membrane currents in human intercostal muscle at varied extracellular potassium. Muscle Nerve 7:465–469

    Google Scholar 

  • Lacerda AE, Kim HS, Ruth P, Perez-Reyes E, Flockerzi V, Hofmann F, Birnbaumer L, Brown AM (1991) Normalization of current kinetics by interaction between the α1 und β subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel. Nature 352:527–530

    Google Scholar 

  • Lamb GD (1992) DHP receptors and excitation-contraction coupling. J Muscle Res Cell Motil 13:394–405

    Google Scholar 

  • Lehmann-Horn F, Rüdel R (1995) Hereditary nondystrophic myotonias and periodic paralyses. Curr Opin Neurol 8:402–410

    Google Scholar 

  • Lehmann-Horn F, Rüdel R, Ricker K, Lorkovic H, Dengler R, Hopf HC (1983) Two cases of adynamia episodica hereditaria: in vitro investigation of muscle cell membrane and contraction parameters. Muscle Nerve 6:113–121

    Google Scholar 

  • Lehmann-Horn F, Küther G, Ricker K, Grafe P, Ballanyi K, Rüdel R (1987a) Adynamia episodica hereditaria with myotonia: a non-inactivating sodium current and the effect of extracellular pH. Muscle Nerve 10:363–374

    Google Scholar 

  • Lehmann-Horn F, Rüdel R, Ricker K (1987b) Membrane defects in paramyotonia congenita (Eulenburg). Muscle Nerve 10:633–641

    Google Scholar 

  • Lehmann-Horn F, Iaizzo PA, Hatt H, Franke C (1991) Altered gating and reduced conductance of single sodium channels in hyperkalemic periodic paralysis. Pflugers Arch 418:297–299

    Google Scholar 

  • Lehmann-Horn F, Rüdel R, Ricker K (1993) Workshop report: non-dystrophic myotonias and periodic paralyses. Neuromuscul Disord 3:161–168

    Google Scholar 

  • Lehmann-Horn F, Engel AG, Ricker K, Rüdel R (1994) The periodic paralyses and paramyotonia congenita. In: Engel AG, Franzini-Armstrong C (eds) Myology, 2nd edn. McGraw-Hill, New York, pp 1303–1334

    Google Scholar 

  • Lehmann-Horn F, Mailänder V, Heine R, George AL (1995a) Myotonia levior is a chloride channel myotonia. Hum Mol Genet 4:1397–1402

    Google Scholar 

  • Lehmann-Horn F, Sipos I, Jurkat-Rott K, Heine R, Brinkmeier H, Fontaine B, Kovacs L, Melzer W (1995b) Altered calcium currents in human hypokalemic periodic paralysis myotubes expressing mutant L-type calcium channels. In: Dawson DC, Frizzell RA (eds) Ion channels and genetic diseases. Rockefeller University Press, New York, pp 101–113

    Google Scholar 

  • Lennox G, Purves A, Marsden D (1992) Myotonia fluctuans. Arch Neurol 49:1010–1011

    Google Scholar 

  • Lerche H, Heine R, Pika U, George AL, Mitrovic N, Browatzki M, Weiß T, Rivet-Bastide M, Franke C, Lomonaco M, Ricker K, Lehmann-Horn F (1993) Human sodium channel myotonia: slowed channel inactivation due to substitutions for glycine within the III/IV linker. J Physiol (Lond) 470:13–22

    Google Scholar 

  • Lerche H, Klugbauer N, Lehmann-Horn F, Hofmann F, Melzer W (1996a) Expression and functional characterization of the cardiac L-type calcium channel carrying a skeletal muscle DHP-receptor mutation causing hypokalaemic periodic. Pflügers Arch 431:461–463

    Google Scholar 

  • Lerche H, Mitrovic N, Dubowitz V, Lehmann-Horn F (1996b) Pathophysiology of paramyotonia congenita: the R1448P sodium channel mutation in adult human skeletal muscle. Ann Neurol 39:599–608

    Google Scholar 

  • Levis R, O'Hare K, Rubin GM (1984) Effects of transposable element insertions on RNA encoded by the white gene of Drosophila. Cell 38:471–481

    Google Scholar 

  • Links TP, Smit AJ, Molenaar WM, Zwarts MJ, Oosterhuis HJGH (1994a) Familial hypokalemic periodic paralysis: clinical, diagnostic and therapeutic aspects. J Neurol Sci 122:33–43

    Google Scholar 

  • Links TP, Vanderhoeven JH, Zwarts MJ (1994b) Surface EMG and muscle fibre conduction during attacks of hypokalaemic periodic paralysis. J Neurol Neurosurg Psychiatry 57:632–634

    Google Scholar 

  • Lipicky RJ (1977) Studies in human myotonic dystrophy. In: Rowland LP (ed) Pathogenesis of human muscular dystrophy. Excerpta Medica, Amsterdam, pp 729–738

    Google Scholar 

  • Lipicky RJ (1979) Myotonic syndromes other than myotonic dystrophy. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 40. Elsevier, Amsterdam, pp 533–571

    Google Scholar 

  • Lipicky RJ, Bryant SH, Salmon JH (1971) Cable parameters, sodium, potassium, chloride, and water content and potassium efflux in isolated external intercostal muscle of normal volunteers and patients with myotonia congenita. J Clin Invest 50:2091–2103

    Google Scholar 

  • Litt M, Kramer P, Browne D, Gancher S, Brunt ERP, Root D, Phromchotikul T, Dubay CJ, Nutt J (1994) A gene for episodic ataxia/myokymia maps to chromosome 12p13. Am J Hum Genet 55:702–709

    Google Scholar 

  • Lorenz C, Meyer-Kleine C, Steinmeyer K, Koch MC, Jentsch TJ (1994) Genomic organization of the human muscle chloride channel ClC-1 and analysis of novel mutations leading to Becker-type myotonia. Hum Mol Genet 3:941–946

    Google Scholar 

  • Loughney K, Kreber R, Ganetzky B (1989) Molecular analysis of the para locus, a sodium channel gene in drosophila. Cell 58:1143–1154

    Google Scholar 

  • MacKinnon R, Aldrich RW, Lee AW (1993) Functional stoichiometry of Shaker potassium channel inactivation. Science 262:757–759

    Google Scholar 

  • MacLennan DH, Phillips MS (1992) Malignant hyperthermia. Science 256:789–794

    Google Scholar 

  • MacLennan DH, Duff C, Zorzato F, Fujii J, Phillips M, Korneluk R, Frodis W, Britt BA, Worton RG (1990) Ryanodine receptor gene is a candidate for predisposition to malignant hyperthermia. Nature 343:559–561

    Google Scholar 

  • Mailänder V, Heine R, Deymeer F, Lehmann-Horn F (1996) Novel chloride channel mutations and their effects on heterozygous carriers. Am J Hum Genet 58:317–324

    Google Scholar 

  • Makita N, Bennett PB Jr, George AL Jr (1994a) Voltage-gated Na+ channel β1 subunit mRNA expressed in adult human skeletal muscle, heart, and brain is encoded by a single gene. J Biol Chem 269:7571–7578

    Google Scholar 

  • Makita N, Sloan-Brown K, Weghuis DO, Ropers HH, George AL Jr (1994b) Genomic organization and chromosomal assignment of the human voltage-gated Na+ channel β1 subunit gene (SCN1B). Genomics 23:628–634

    Google Scholar 

  • Malo MS, Blanchard BJ, Andresen JM, Srivastava K, Chen XN, Li X, Wang E, Korenberg JR, Ingram VM (1994a) Localisation of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24. Cytogenet Cell Genet 67:178–186

    Google Scholar 

  • Malo MS, Srivastava K, Andresen JM, Chen XN, Korenberg JR, Ingram VM (1994b) Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31. Proc Natl Acad Sci USA 91:2975–2979

    Google Scholar 

  • Malouf NN, McMahon DK, Heinsworth CN, Kay BK (1992) A two-motif isoform of the major calcium channel subunit in skeletal muscle. Neuron 8:899–906

    Google Scholar 

  • Mason K (1988) A hereditary disease in burmese cats manifested as an episodic weakness with head nodding and neck ventroflexion. J Am Anim Hospital Ass 24:147–151

    Google Scholar 

  • McCarthy TV, Healy JMS, Lehane M, Heffron JJA, Deufel T, Lehmann-Horn F, Farrall M, Johnson K (1990) Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q11.2–13.2. Nature 343:562–563

    Google Scholar 

  • McClatchey AI, Lin CS, Wang J, Hoffman EP, Rojas C, Gusella JF (1992a) The genomic structure of the human skeletal muscle sodium channel gene. Hum Mol Genet 1:521–527

    Google Scholar 

  • McClatchey AI, McKenna-Yasek D, Cros D, Worthen HG, Kuncl RW, DeSilva SM, Cornblath DR, Gusella JF, Brown RH Jr (1992b) Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. Nat Genet 2:148–152

    Google Scholar 

  • McClatchey AI, van den Bergh P, Pericak-Vance MA, Raskind W, Verellen C, McKenna-Yasek D, Rao K, Haines JL, Bird T, Brown RH Jr, Gusella JF (1992c) Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. Cell 68:769–774

    Google Scholar 

  • McClatchey AI, Cannon SC, Slaugenhaupt SA, Gusella JF (1993) The cloning and expression of a sodium channel β-1-subunit cDNA from human brain. Hum Mol Genet 2:745–749

    Google Scholar 

  • McKusick VA (1992) Mendelian inheritance in man. Hopkins University Press, Baltimore

    Google Scholar 

  • Mehrke G, Brinkmeier H, Jockusch H (1988) The myotonic mouse mutant ADR: electrophysiology of the muscle fiber. Muscle Nerve 11:440–446

    Google Scholar 

  • Melzer W, Herrmann-Frank A, Lüttgau HC (1995) The role of Ca2+ ions in excitation-contraction coupling of skeletal muscle fibres. Biochim Biophys Acta 1241:59–116

    Google Scholar 

  • Meyer-Kleine C, Otto M, Zoll B, Koch MC (1994a) Molecular and genetic characterisation of German families with paramyotonia congenita and demonstration of founder effect in the Ravensberg families. Hum Genet 93:707–710

    Google Scholar 

  • Meyer-Kleine C, Ricker K, Otto M, Koch MC (1994b) A recurrent 14 bp deletion in the CLCN1 gene associated with generalized myotonia (Becker). Hum Mol Genet 3:1015–1016

    Google Scholar 

  • Meyer-Kleine C, Steinmeyer K, Ricker K, Jentsch TJ, Koch MC (1995) Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCNI) leading to myotonia. Am J Hum Genet 57:1325–1334

    Google Scholar 

  • Middleton RE, Pheasant DJ, Miller C (1994) Purification, reconstitution, and subunit composition of a voltage-gated chloride channel from Torpedo electroplax. Biochemistry 33:13189–13198

    Google Scholar 

  • Mikami A, Imoto K, Tanabe T, Niidome T, Mori Y, Takeshima H, Narumiya S, Numa S (1989) Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel. Nature 340:230–233

    Google Scholar 

  • Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME (1992) P-type calcium channels blocked by the spider toxin θ-Aga-IVA. Nature 355:827–30

    Google Scholar 

  • Mitchell G, Heffron JJA (1982) Porcine stress syndrome. Adv Food Res 28:167–230

    Google Scholar 

  • Mitrovic N, George AL Jr, Heine R, Wagner S, Pika U, Hartlaub U, Zhou M, Lerche H, Fahlke C, Lehmann-Horn F (1994) Potassium-aggravated myotonia: the V1589 M mutation destabilizes the inactivated state of the human muscle sodium channel. J Physiol (Lond) 478:395–402

    Google Scholar 

  • Mitrovic N, George AL Jr, Heine R, Lehmann-Horn F (1995) Potassium-aggravated myotonia: biophysical and clinical implications of the G1306A/V/E human muscle sodium channel mutations. J Physiol (Lond) 487:107–114

    Google Scholar 

  • Mitrovic N, Lerche H, Heine R, Fleischhauer R, Pika-Hartlaub U, Hartlaub U, George Jr AL, Lehmann-Horn F. Role in fast inactivation of conserved amino acids in the IV/S4–S5 loop of the human muscle Na+ channel. Neuroscience Letters, in press (1996)

    Google Scholar 

  • Moorman JR, Kirsch GE, VanDongen AMJ, Joho RH, Brown AM (1990) Fast and slow gating of sodium channels encoded by a single mRNA. Neuron 4:243–252

    Google Scholar 

  • Neumann P, Weber T (1989) Mouse News Lett 83:157

    Google Scholar 

  • Nilius B (1988) Modal gating behavior of cardiac sodium channels in cell-free membrane patches. Biophys J 53:857–862

    Google Scholar 

  • Noda M, Suzuki H, Numa S, Stühmer W (1989) A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II. FEBS Lett 259:213–216

    Google Scholar 

  • Nowycky MC, Fox AP, Tsien RW (1985) Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 316:440–443

    Google Scholar 

  • Palade PT, Barchi RL (1977) On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids. J Gen Physiol 69:879–896

    Google Scholar 

  • Patlak J, Ortiz M (1986) Two modes of gating during late Na+ channel currents in frog sartorius muscle. J Gen Physiol 87:305–326

    Google Scholar 

  • Patton DE, West JW, Catterall WA, Goldin AL (1992) Amino acid residues required for fast Na+-channel inactivation: charge neutralizations and deletions in the III–IV linker. Proc Natl Acad Sci USA 89:10905–10909

    Google Scholar 

  • Patton DE, West JW, Catterall WA, Goldin AL (1993) A peptide segment critical for sodium channel inactivation functions as an inactivation gate in a potassium channel. Neuron 11:967–974

    Google Scholar 

  • Pelzer S, Sieber M, Hofmann F, Trautwein W (1989) Calcium channels reconstituted from the skeletal muscle dihydropyridine receptor protein complex and its α1 peptide subunit in lipid bilayers. Ann NY Acad Sci 560:138–154

    Google Scholar 

  • Perez-Reyes E, Castellano A, Haeyoung SK, Bertrand P, Baggstrom E, Lacerda AE, Wei X, Birnbaumer L (1992) Cloning and expression of a cardiac/brain β subunit of the L-type calcium channel. J Biol Chem 267:1792–1797

    Google Scholar 

  • Pickar JG, Spier SJ, Snyder JR, Carlsen RC (1991) Altered ionic permeability in skeletal muscle from horses with hyperkalemic periodic paralysis. Am J Physiol 260:C92–C933

    Google Scholar 

  • Plassart E, Reboul J, Rime C-S, Recan D, Millasseau P, Eymard B, Pelletier J, Thomas C, Chapon F, Desnuelle C, Confavreux C, Bady B, Martin J-J, Lenoir G, Serratrice G, Fardeau M, Fontaine B (1994) Mutations in the muscle sodium channel gene (SCN4A) in 13 French families with hyperkalemic periodic paralysis and paramyotonia congenita: phenotype to genotype correlations and demonstration of the predominance of two mutations. Eur J Hum Genet 2:110–124

    Google Scholar 

  • Pongs O (1992) Molecular biology of voltage-dependent potassium channels. Physiol Rev 72:S69–S88

    Google Scholar 

  • Poskanzer DC, Kerr DNS (1961) A third type of periodic paralysis with normokalemia and favourable response to sodium chloride. Am J Med 31:328–342

    Google Scholar 

  • Potts JF, Regan MR, Rochelle JM, Seldin MF, Agnew WS (1993) A glial-specific voltage-sensitive Na channel gene maps close to clustered genes for neuronal isoforms on mouse chromosome 2. Biochem Biophys Res Commun 197:100–107

    Google Scholar 

  • Powers PA, Gregg RG, Lalley P, Liao M, Hogan K (1991) Assignment of the human gene for the α1 subunit of the cardiac DHP-sensitive Ca2+ channel to chromosome 12p12-pter. Genomics 10:835–839

    Google Scholar 

  • Powers PA, Liu S, Hogan K, Gregg RG (1992) Skeletal muscle and brain isoforms of a β-subunit of human voltage-dependent calcium channels are encoded by a single gene. J Biol Chem 267:22967–22972

    Google Scholar 

  • Powers PA, Liu S, Hogan K, Gregg RG (1993) Molecular characterization of the gene encoding the γ subunit of the human skeletal muscle 1,4-dihydropyridine-sensitive Ca2+ channel (CACNLG), cDNA sequence, gene structure, and chromosomal location. J Biol Chem 268:9275–9279

    Google Scholar 

  • Powers PA, Scherer SW, Tsui L-C, Gregg RG, Hogan K (1994) Localization of the gene encoding the α2/δ subunit (CACNL2A) of the human skeletal muscle voltage-dependent Ca2+ channel to chromosome 7q21–q22 by somatic cell hybrid analysis. Genomics 19:192–193

    Google Scholar 

  • Pragnell M, Sakamoto J, Jay SD, Campbell KP (1991) Cloning and tissue-specific expression of the brain calcium channel β-subunit. FEBS Lett 291:253–258

    Google Scholar 

  • Ptáček LJ, George AL Jr, Griggs RC, Tawil R, Kallen RG, Barchi RL, Robertson M, Leppert MF (1991a) Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell 7:1021–1027

    Google Scholar 

  • Ptáček LJ, Trimmer JS, Agnew WS, Roberts JW, Petajan JH, Leppert M (1991b) Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium channel gene locus. Am J Hum Genet 49:851–854

    Google Scholar 

  • Ptáček LJ, George AL Jr, Barchi RL, Griggs RC, Riggs JE, Robertson M, Leppert MF (1992a) Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita. Neuron 8:891–897

    Google Scholar 

  • Ptáček LJ, Tawil R, Griggs RC, Storvick D, Leppert M (1992b) Linkage of atypical myotonia congenita to sodium channel locus. Neurology 42:431–433

    Google Scholar 

  • Ptáček LJ, Gouw L, Kwiecinski H, McManis P, Mendell JR, Barohn RJ, George AL, Barchi RL, Robertson M, Leppert M (1993) Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis. Ann Neurol 33:300–307

    Google Scholar 

  • Ptáček L, Tawil R, Griggs RC, Engel A, Layzer RB, Kwiecinski H, McManis PG, Santiago L, Moore M, Fouad G, Bradley P, Leppert MF (1994a) Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell 77:863–868

    Google Scholar 

  • Ptáček LJ, Tawil R, Griggs RC, Meola G, McManis P, Barohn RJ, Mendell JR, Harris C, Spitzer R, Santiago F, Leppert MF (1994b) Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita and hyperkalemic periodic paralysis. Neurology 44:1500–1503

    Google Scholar 

  • Pusch M, Jentsch TJ (1994) Molecular physiology of voltage-gated chloride channels. Physiol Rev 74:813–827

    Google Scholar 

  • Pusch M, Steinmeyer K, Jentsch TJ (1994) Low single channel conductance of the major skeletal muscle chloride channel, ClC-1. Biophys J 66:149–152

    Google Scholar 

  • Reininghaus J, Füchtbauer EM, Bertram K, Jockusch H (1988) The myotonic mouse mutant ADR: physiological and histochemical properties of muscle. Muscle Nerve 11:433–439

    Google Scholar 

  • Ricker K, Camacho L, Grafe P, Lehmann-Horn F, Rüdel R (1989) Adynamia episodica hereditaria: what causes the weakness? Muscle Nerve 10:883–891

    Google Scholar 

  • Ricker K, Lehmann-Horn F, Moxley RT (1990) Myotonia fluctuans. Arch Neurol 47:268–272

    Google Scholar 

  • Ricker K, Moxley RT, Heine R, Lehmann-Horn F (1994) Myotonia fluctuans, a third type of muscle sodium channel disease. Arch Neurol 51:1095–1102

    Google Scholar 

  • Rivet M, Cognard C, Imbert N, Rideau Y, Duport G, Raymond G (1992) A third type of calcium current in cultured human skeletal muscle cells. Neurosci Lett 138:97–102

    Google Scholar 

  • Rogart RB, Cribbs LL, Muglia LK, Kephart DD, Kaiser MW (1989) Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform. Proc Natl Acad Sci USA 86:8170–8174

    Google Scholar 

  • Rojas CV, Wang J, Schwartz L, Hoffman EP, Powell BR, Brown RH Jr (1991) A Met-to-Val mutation in the skeletal muscle sodium channel alpha-subunit in hyperkalemic periodic paralysis. Nature 354:387–389

    Google Scholar 

  • Romey G, García L, Dimitriadou V, Pincon-Raymond M, Rieger F, Lazdunski M (1989) Ontogenesis and localization of Ca2+ channels in mammalian skeletal muscle in culture and role in excitation-contraction coupling. Proc Natl Acad Sci USA 86:2933–2937

    Google Scholar 

  • Rosenbohm A, Rüdel R, George AL Jr, Fahlke C (1996) Regulation of the human muscle chloride channel, hClC-1, by protein kinase C. J Neurosci (submitted)

    Google Scholar 

  • Rüdel R (1990) The myotonic mouse — a realistic model for the study of human recessive generalized myotonia. Trends Neurosci 13:1–3

    Google Scholar 

  • Rüdel R, Dengler R, Ricker K, Haass A, Emser W (1980) Improved therapy of myotonia with the lidocaine derivative tocainide. J Neurol 222:275–278

    Google Scholar 

  • Rüdel R, Lehmann-Horn F, Ricker K, Küther G (1984) Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters. Muscle Nerve 7:110–120

    Google Scholar 

  • Rüdel R, Ricker K, Lehmann-Horn F (1988) Transient weakness and altered membrane characteristic in recessive generalized myotonia (Becker). Muscle Nerve 11:202–211

    Google Scholar 

  • Rüdel R, Ricker K, Lehmann-Horn F (1993) Genotype-phenotype correlations in human skeletal muscle sodium chanel diseases. Arch Neurol 50:1241–1248

    Google Scholar 

  • Rüdel R, Lehmann-Horn F, Ricker K (1994) The non-progressive myotonias. In: Engel AG, Franzini-Armstrong C (eds) Myology, 2nd edn. McGraw-Hill, New York, pp 1291–1303

    Google Scholar 

  • Rudolph JA, Spier SJ, Byrns G, Hoffmann EP (1992a) Linkage of hyperkalemic periodic paralysis in Quarter Horses to the horse adult skeletal muscle sodium channel gene. Anim Genet 23:241–250

    Google Scholar 

  • Rudolph JA, Spier SJ, Byrns G, Rojas CV, Bernoco D, Hoffman EP (1992b) Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding. Nat Genet 2:144–147

    Google Scholar 

  • Rudy B (1988) Diversity and ubiquity of K channels. Neuroscience 25:729–749

    Google Scholar 

  • Ruth P, Röhrkasten A, Biel M, Bosse E, Regulla S, Meyer HE, Flockerzi V, Hofmann F (1989) Primary structure of the β subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 245:1115–1118

    Google Scholar 

  • Saint DA, Ju YK, Gage PW (1992) A persistent sodium current in rat ventricular myocytes. J Physiol (Lond) 454:219–231

    Google Scholar 

  • Salkoff L, Baker K, Butler A, Covarrubias M, Pak MD, Wei A (1992) An essential "set" of K+ channels conserved in flies, mice and humans. Trends Neurosci 15:161–166

    Google Scholar 

  • Sanguinetti MC, Jiang C, Curran ME, Keating MT (1995) A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81:299–307

    Google Scholar 

  • Satin J, Kyle JW, Chen M, Bell P, Cribbs LL, Fozzard HA, Rogart RB (1992) A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties. Science 256:1202–1205

    Google Scholar 

  • Schreibmayer W, Wallner M, Lotan I (1994) Mechanism of modulation of single sodium channels from skeletal muscle by the β1-subunit from rat brain. Pflugers Arch 426:360–362

    Google Scholar 

  • Schultz D, Mikala G, Yatani A, Engle DB, Iles DE, Segers B, Sinke RJ, Weghuis DO, Klöckner U, Wakamori M, Wang J-J, Melvin D, Varadi G, Schwartz A (1993) Cloning, chromosomal localization, and functional expression of the α1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci USA 90:6228–6232

    Google Scholar 

  • Seino S, Chen L, Seino M, Blondel O, Takeda J, Johnson JH, Bell GI (1992a) Cloning of the α1 subunit of a voltage-dependent clacium channel expressed in pancreatic β cells. Proc Natl Acad Sci USA 89:584–588

    Google Scholar 

  • Seino S, Yamada Y, Espinosa III R, Le Beau MM, Graeme IB (1992b) Assignment of the gene encoding the α1 subunit of the neuroendocrine/brain-type calcium channel (CACNL1A2) to human chromosome 3, band p14.3. Genomics 13:1375–1357

    Google Scholar 

  • Singer D, Biel M, Lotan I, Flockerzi V, Hofmann F, Dascal N (1991) The roles of the subunits in the function of the calcium channel. Science 253:1553–1556

    Google Scholar 

  • Sipos I, Melzer W (1995) Calcium currents in cultured human skeletal muscle cells. Pflugers Arch 426:R85

    Google Scholar 

  • Sipos I, Jurkat-Rott K, Harasztosi CS, Fontaine B, Kovacs L, Melzer W, Lehmann-Horn F (1995) Skeletal muscle DHP receptor mutations alter calcium currents in human hypokalaemic periodic paralysis myotubes. J Physiol (Lond) 483:299–306

    Google Scholar 

  • Spaans F, Theunissen P, Reekers A, Smit L, Veldman H (1990) Schwartz-Jampel syndrome: part I. Clinical, electromyographic, and histologic studies. Muscle Nerve 13:516–527

    Google Scholar 

  • Steinmeyer K, Klocke R, Ortland C, Gronemeier M, Jockusch H, Gründer S, Jentsch TJ (1991a) Inactivation of muscle chloride channel by transposon insertion in myotonic mice. Nature 354:304–308

    Google Scholar 

  • Steinmeyer K, Ortland C, Jentsch TJ (1991b) Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel. Nature 354:301–304

    Google Scholar 

  • Steinmeyer K, Lorenz C, Pusch M, Koch MC, Jentsch TJ (1994) Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen). EMBO J 13:737–743

    Google Scholar 

  • Stühmer W, Conti F, Suzuki H, Wang X, Noda M, Yahagi N, Kubo H, Numa S (1989) Structural parts involved in activation and inactivation of the sodium channel. Nature 339:597–603

    Google Scholar 

  • Tahmoush A, Schaller KL, Zhang P, Hyslop T, Heiman-Patterson T, Caldwell JH (1994) Muscle sodium channel inactivation defect in paramyotonia congenita with the Thr1313Met mutation. Neuromuscul Disord 4:447–454

    Google Scholar 

  • Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S (1987) Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature 328:313–318

    Google Scholar 

  • Tanabe T, Beam KG, Powell JA, Numa S (1988) Restoration of excitation-contraction coupling and slow calcium current in dysgenic muscle by dihydropyridine receptor complementary DNA. Nature 336:134–139

    Google Scholar 

  • Terlau H, Heinemann SH, Stühmer W, Pusch M, Conti F, Imoto K, Numa S (1991) Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II. FEBS Lett 293:93–96

    Google Scholar 

  • Thiemann A, Gründer S, Pusch M, Jentsch TJ (1992) A chloride channel widely expressed in epithelial and non-epithelial cells. Nature 356:57–60

    Google Scholar 

  • Thomasen E (1948) Myotonia. Universitätsforlaget, Aarhus

    Google Scholar 

  • Thomsen J (1876) Tonische Krämpfe in willkürlich beweglichen Muskeln in Folge von ererbter psychischer Disposition. Arch Psychiatr Nervenkrankheiten 6:702–718

    Google Scholar 

  • Trimmer JS, Cooperman SS, Tomiko SA, Zhou J, Crean SM, Boyle MB, Kallen RG, Sheng Z, Barchi RL, Sigworth FJ, Goodman RH, Agnew WS, Mandel G (1989) Primary structure and functional expression of mammalian skeletal muscle sodium channel. Neuron 3:33–49

    Google Scholar 

  • Trudell RG, Kaiser KK, Griggs RC (1987) Acetazolamide responsive myotonia congenita. Neurology 37:488–491

    Google Scholar 

  • Tyler FH, Stephens FE, Gunn FD, Perkoff GT (1951) Studies in disorders of muscle. VII. Clinical manifestations and inheritance of a type of periodic paralysis without hypopotassemia. J Clin Invest 30:492–502

    Google Scholar 

  • Uchida S, Sasaki S, Furukawa T, Hiraoka M, Imai T, Hirata Y, Marumo F (1993) Molecular cloning of a chloride channel that is regulated by dehydration and expressed predominantly in kidney medulla. J Biol Chem 268:3821–3824

    Google Scholar 

  • Ukomadu C, Zhou J, Sigworth FJ, Agnew WF (1992) µ1 Na+ channels expressed transiently in human embryonic kidney cells: biochemical and biophysical properties. Neuron 8:663–676

    Google Scholar 

  • Vahedi K, Joutel A, Van Bogaert P, Ducros A, Maciazeck J, Bach JF, Bousser MG, Tournier-Lasserve E (1995) A gene for hereditary paroxysmal cerebellar ataxia maps to chromosone 19p. Ann Neurol 37:289–293

    Google Scholar 

  • van Slegtenhorst MA, Bassi MT, Borsani G, Wapenaar MC, Ferrero GB, de Concillis L, Rugarli EI, Grillo A, Franco B, Zoghbi HY, Ballabio A (1994) A gene from the Xp22.3 region shares homology with voltage-gated chloride channels. Hum Mol Genet 3:547–552

    Google Scholar 

  • Varadi G, Lory P, Schultz D, Varadi M, Schwartz A (1991) Acceleration of activation and inactivation by the β subunit of the skeletal muscle calcium channel. Nature 352:159–162

    Google Scholar 

  • Vassilev PM, Scheuer T, Catterall WA (1988) Identification of an intracellular peptide segment involved in sodium channel inactivation. Science 241:1658–1661

    Google Scholar 

  • Vassilev P, Scheuer T, Catterall WA (1989) Inhibition of inactivation of single sodium channels by a site-directed antibody. Proc Natl Acad Sci USA 86:8147–8151

    Google Scholar 

  • Vita GM, Olckers A, Jedlicka AE, George AL, Heiman-Patterson T, Rosenberg H, Fletcher JE, Levitt RC (1995) Masseter muscle rigidity associated with glycine1306-to-alanine mutation in adult muscle sodium channel α-subunit gene. Anesthesiology 82:1097–1103

    Google Scholar 

  • Wallner M, Weigl L, Meera P, Lotan I (1993) Modulation of the skeletal muscle sodium channel α-subunit by the β1-subunit. FEBS Lett 336:535–539

    Google Scholar 

  • Wang J, Rojas CV, Zhou J, Schwartz LS, Nicholas H, Hoffman EP (1992) Sequence and genomic structure of the human adult skeletal muscle sodium channel α subunit gene on 17q. Biochem Biophys Res Commun 182:794–801

    Google Scholar 

  • Wang J, Zhou J, Todorovic SM, Feero WG, Barany F, Conwit R, Hausmanowa-Petrusewicz I, Fidzianska A, Arahata K, Wessel HB, Hartladge P, Ricker K, Lehmann-Horn F, Hayakawa H, Hoffman EP (1993) Molecular genetic and genetic correlations in sodium channelopathies: lack of founder effect and evidence for a second gene. Am J Hum Genet 52:1074–1084

    Google Scholar 

  • Wang J, Dubowitz V, Lehmann-Horn F, Ricker K, Michaels J, Ptáček LJ, Hoffman EP (1995) In vivo structure/function studies: consecutive Arg1448 changes to Cys, His and Pro at the extracellular surface of IVS4. In: Proceedings of the society of general physiologists. Rockefeller University Press, New York, pp 77–88

    Google Scholar 

  • Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT (1995) SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80:805–811

    Google Scholar 

  • Watkins WJ, Watts DC (1984) Biological features of the new A2G-adr mouse with abnormal muscle function. Lab Anim 18:1–6

    Google Scholar 

  • Wei X, Perez-Reyes E, Lacerda AE, Schuster G, Brown AM, Birnbaumer L (1991) Heterologous regulation of the cardiac Ca2+ channel α1 subunit by skeletal muscle β and γ subunits. J Biol Chem 266:21943–21947

    Google Scholar 

  • West JW, Patton DE, Scheuer T, Wang Y, Goldin AL, Catterall WA (1992) A cluster of hydrophobic amino acid residues required for fast Na+ channel inactivation. Proc Natl Acad Sci USA 89:10910–10914

    Google Scholar 

  • White MM, Miller C (1979) A voltage-gated anion channel from the electric organ of Torpedo californica. J Biol Chem 254:10161–10166

    Google Scholar 

  • White GR, Plaskett J (1904) "Nervous,", "stiff-legged," or "fainting" goats. Am Vet Rev 28:556–560

    Google Scholar 

  • Williams ME, Feldman DH, McCue AF, Brenner R, Velicelebi G, Ellis SB, Harpold MM (1992) Structure and functional expression of α1, α2 and β subunits of a novel human neuronal calcium channel subtype. Neuron 8:71–84

    Google Scholar 

  • Wischmeyer E, Nolte E, Klocke R, Jockusch H, Brinkmeier H (1993) Development of electrical myotonia in the adr mouse: role of chloride conductance in myotubes and neonatal animals. Neuromuscul Disord 3:267–274

    Google Scholar 

  • Wischmeyer E, Weber-Schürholz S, Jockusch H (1995) Sarcolemmal chloride and potassium channels from normal and myotonic mouse muscle studied in lipid supplemented vesicles. Biochem Biophys Res Commun 213:513–518

    Google Scholar 

  • Yang N, Horn R (1995) Evidence for voltage-dependent S4 movement in sodium channels. Neuron 15:213–218

    Google Scholar 

  • Yang N, Ji S, Zhou M, Ptáček LJ, Barchi RL, Horn R, George AL Jr (1994) Sodium channel mutations in paramyotonia congenita exhibit similar biophysical phenotypes in vitro. Proc Natl Acad Sci USA 91:12785–12789

    Google Scholar 

  • Yellen G, Jurman ME, Abramson T, MacKinnon R (1991) Mutations affecting internal TEA blockade identify the probable pore-forming region of a K+ channel. Science 251:939–942

    Google Scholar 

  • Zhou J, Potts JF, Trimmer JS, Agnew WS, Sigworth FJ (1991) Multiple gating modes and the effect of modulating factors of the µ1 sodium channel. Neuron 7:775–785

    Google Scholar 

  • Zhou J, Spier SJ, Beech J, Hoffman EP (1994) Pathophysiology of sodium channelo-pathies: correlation of normal/mutant mRNA ratios with clinical phenotype in dominantly-inherited periodic paralysis. Hum Mol Genet 3:1599–1603

    Google Scholar 

  • Zierler KL, Andres R (1957) Movement of potassium into skeletal muscle during spontaneous attack in family periodic paralysis. J Clin Invest 36:730–737

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, University of Ulm, 89069, Ulm, Germany

    F. Lehmann-Horn & R. Rüdel

Authors
  1. F. Lehmann-Horn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Rüdel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag

About this chapter

Cite this chapter

Lehmann-Horn, F., Rüdel, R. (1996). Molecular pathophysiology of voltage-gated ion channels. In: Reviews of Physiology Biochemistry and Pharmacology, Volume 128. Reviews of Physiology, Biochemistry and Pharmacology, vol 128. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-61343-9_9

Download citation

  • DOI: https://doi.org/10.1007/3-540-61343-9_9

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-61343-5

  • Online ISBN: 978-3-540-68502-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation