Abstract
Apamin is a neurotoxin extracted from bee venom (Habermann 1972). It is a polypeptide of 18 amino acids with two disulfide bridges (Fig. 1). It is the only polypeptide neurotoxin, as far as we know, that crosses the blood-brain barrier. Analysis of the structure-function relationships of this toxin has shown that two of the 18 amino acids in the sequence have particular importance for the action of the toxin; they are Arg-13 and Arg-14 (Vincent et al. 1975). These two residues seem to be essential elements of the active site of the toxin. Chemical modifications elsewhere in the sequence may decrease the toxicity of the polypeptide, but do not suppress its biologic activity. Cumulative chemical modifications — of the amino group and of the imidazole of His-18 for example — may, however, abolish the activity of the toxin (Vincent et al. 1975). Solid phase synthesis of apamin and analogs has been carried out (Cosand and Merrifield 1977; Granier et al. 1978). This approach has confirmed that the active site of apamin comprises the two residues Arg-13 and Arg-14. The exact three-dimensional structure of the toxin remains unknown. However, recent solution analysis of apamin by NMR techniques has suggested that the toxin is highly ordered with an α-helical core and regions of β-type turns (Bystrov et al. 1980; Wemmer and Kallenbach 1983).
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References
Adams PR, Constanti A, Brown DA, Clark RB (1982) Fast voltage-sensitive potassium current in vertebrate sympathetic neurons. Nature 296:746–749
Banks BEC, Brown C, Burgess GM, Burnstock G, Claret M, Cocks TM, Jenkinson DH (1979) Apamin blocks certain neurotransmitter-induced increases in potassium permeability. Nature 282:415–417
Barchi RL, Cohen SA, Murphy LE (1980) Purification from rat sarcolemma of the saxi-toxin binding component of the excitable membrane sodium channel. Proc Natl Acad Sci USA 77:1306–1310
Barhanin J, Pauron D, Lombet A, Norman RI, Vijverberg HPM, Giglio JR, Lazdunski M (1983 a) Electrophysiological characterization, solubilization and purification of the Tityus γ toxin receptor associated with the gating component of the Na+ channel from rat brain. EMBO J 2:915–920
Barhanin J, Schmid A, Lombet A, Wheeler KP, Lazdunski M (1983 b) Molecular size of different neurotoxin receptors on the voltage-sensitive Na+ channel. J Biol Chem 258:700–702
Barrett JN, Barrett EF, Dribbin LB (1981) Calcium-dependent slow potassium conductance in rat skeletal myotubules. Dev Biol 82:258–266
Barrett JN, Magleby KL, Pallotta BS (1982) Properties of single calcium-activated potassium channels in cultured rat muscle. J Physiol (London) 331:211–230
Bystrov VF, Okhanov VV, Miroshnikov AI, Ovchinnikov YA (1980) Solution spatial structure of apamin as derived from NMR study. FEBS Lett 119:113–117
Cook NS, Haylett DN, Strong P (1983) High affinity binding of 125I-monoiodo apamin to isolated guinea-pig hepatocytes. FEBS Lett 152:265–269
Cosand WL, Merrifield RB (1977) Concept of internal structural controls for evaluation of inactive synthetic peptide analog: synthesis of (ORN 13,14) apamin and its guanidi-nation to an apamin derivative with full neurotoxic activity. Proc Natl Acad Sci USA 74:2771–2775
Fosset M, Schmid-Antomarchi H, Hugues M, Romey G, Lazdunski M (1984) The presence in pig brain of an endogenous equivalent of apamin, the bee venom peptide which specifically blocks Ca2+-dependent K+ channels. Proc Natl Acad Sci USA 81:7228–7232
Granier C, Pedroso Muller E, Van Rietschoten J (1978) Use of synthetic analogs for a study on the structure-activity relationship of apamin. Eur J Biochem 82:293–299
Grimm T (1975) The ages of onset and the age of death in patients with dystrophia myotonia. J Hum Genet 23:301–308
Gruener R (1977) In vitro membrane excitability of diseased human muscles. In: Rowland LP (ed) Pathogenesis of human muscular dystrophy. Excerpta Medica, Amsterdam, p242
Gruener R, Stern LZ, Payne C, Hannapel L (1975) Hyperthyroid myopathy intracellular electrophysiological measurements in biopsied human intercostal muscle. J Neuro Sci 24:339–349
Gruener R, Stern LZ, Markovitz D, Gerdes C (1979) Electrophysiologic properties of intercostal muscle fibers in human neuromuscular diseases. Muscle Nerve 2:165–172
Habermann E (1972) Bee and wasp venom. Science 177:314–322
Habermann E, Fischer K (1979) Bee venom neurotoxin (apamin): iodine labelling and characterization of binding sites. Eur J Biochem 94:355–364
Hartshorne RP, Catterall WA (1981) Purification of the saxitoxin receptor of the sodium channel from rat brain. Proc Natl Acad Sci USA 78:4620–4624
Hugues M, Romey G, Duval D, Vincent JP, Lazdunski M (1982 a) Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells: voltage-clamp and biochemical characterization of the toxin receptor. Proc Natl Acad Sci USA 79:1308–1312
Hugues M, Schmid H, Romey G, Duval D, Freiin C, Lazdunski M (1982 b) The calcium-dependent slow potassium conductance in cultured rat muscle cells: characterization with apamin. EMBO J 9:1039–1042
Hugues M, Duval D, Kitabgi P, Lazdunski M, Vincent JP (1982 c) Preparation of a pure monoiodo derivative of the bee venom neurotoxin apamin and its binding properties to rat brain synaptosomes. J Biol Chem 257:2762–2769
Hugues M, Duval D, Schmid H, Kitabgi P, Lazdunski M (1982d) Specific binding and pharmacological interactions of apamin, the neurotoxin from bee venom, with guinea-pig colon. Life Sci 31:437–443
Hugues M, Schmid H, Lazdunski M (1982 e) Identification of a protein component of the calcium-dependent potassium channel by affinity labelling with apamin. Biochem Bio-phys Res Commun 107:1577–1582
Latorre R, Vergara C, Hidalgo C (1982) Reconstitution in planar lipid bilayers of a calcium-dependent potassium channel from transverse tubule membranes isolated from rabbit skeletal muscle. Proc Natl Acad Sci USA 79:805–809
Lazdunski M, Renaud JF (1982) The action of cardiotoxins on cardiac plasma membranes. Annu Rev Physiol 44:463–473
Levinson SR, Ellory JC (1973) Molecular size of the tetrodotoxin binding site estimated by irradiation inactivation. Nature 245:122–123
Lipicky RJ (1977) Studies in human myotonic dystrophy. In: Rowland LP (ed) Pathogenesis of human muscular dystrophy. Excerpta Medica, Amsterdam, p 729
Maas AD, Den Hertog A (1979) The effect of apamin on the smooth muscle cells of the guinea-pig taenia coli. Eur J Pharmacol 58:151–156
Maas AD, Den Hertog A, Ras R, Van Den Akker J (1980) The action of apamin on guinea-pig taenia caeci. Eur J Pharmacol 67:265–274
Marty A (1981) Calcium-dependent potassium channels with large unitary conductance in chromaffin cell membranes. Nature 291:497–500
McComas AJ, Mrozek K (1968) The electrical properties of muscle fiber membranes in dystrophic myotonia and myotonia congenita. J Neurol Neurosurg Psychiatry 31:441–447
Merickel M, Gray R, Chauvin P, Appel S (1981) Cultured muscle from myotonic muscular dystrophy patients: altered membrane electrical properties. Proc Natl Acad Sci USA 78:648–652
Methfessel C, Boheim G (1982) The gating of single calcium-dependent potassium channel is described by an activation blockade mechanism. Biophys Struct Mech 9:35–60
Moore HPM, Fritz LC, Raftery MA, Brokes JP (1982) Isolation and characterization of a monoclonal antibody against the saxitoxin-binding component from the electric organ of the eel Electrophorus electricus. Proc Natl Acad Sci USA 79:1673–1677
Mourre C, Schmid-Antomarchi H, Hugues M, Lazdunski M (1984) Autoradiographic localization of apamin-sensitive Ca2+-dependent K+ channels in rat brain. Eur J Pharmacol 100:135–136
Mourre C, Hugues M, Lazdunski M (1986) Quantitative autoradiographic mapping in rat brain of the receptor of apamin, a polypeptide toxin specific for one class of Ca2+-dependent K+ channel. Brain Res 382:239–249
Neher E, Sakmann B, Steinbach JH (1978) The extracellular patch-clamp: a method for resolving current through individual open channels in biological membranes. Pflugers Arch 375:219–228
Norman RI, Schmid A, Lombet A, Barhanin J, Lazdunski M (1983) Purification of binding protein for Tityus y toxin identified with the gating component of the voltage-sensitive Na+ channel. Proc Natl Acad Sci USA 80:4164–4168
Pennefather P, Lancaster B, Adams PR, Nicoll RA (1985) Two distinct Ca-dependent K currents in bullfrog sympathetic ganglion cells. Proc Natl Acad Sci USA 82:3040–3044
Renaud JF, Desnuelle C, Schmid-Antomarchi H, Hugues M, Serratrice G, Lazdunski M (1986) Expression of the apamin receptor in muscles of patients with myotonic muscular dystrophy. Nature 319:678–680
Romey G, Lazdunski M (1984) The coexistence in rat muscle cells of two distinct classes of Ca2+-dependent K+ channels with different pharmacological properties and different physiological functions. Biochem Biophys Res Commun 118:669–674
Rudel R, Lehmann-Horn F (1985) Membrane changes in cells from myotonia patients. Physiol Rev 65:310–356
Schmid-Antomarchi H, Hugues M, Norman RI, Ellory JC, Borsotto M, Lazdunski M (1984) Molecular properties of the apamin-sensitive Ca2+-dependent K+ channel: radiation-inactivation, affinity labelling and solubilization. Eur J Biochem 142:1–6
Schmid-Antomarchi H, Renaud JF, Romey G, Hugues M, Schmid A, Lazdunski M (1985) The all-or-none role of innervation in the expression of the apamin-sensitive Ca2+-activated K+ channel in mammalian skeletal muscle. Proc Natl Acad Sci USA 82:2188–2195
Schweitz H, Lazdunski M (1984) A microradioimmunoassay for apamin. Toxicon 22:985–988
Seagar MJ, Labbé-Julié C, Granier C, Van Rietshoten J, Couraud F (1985) Photoaffinity labeling of components of the apamin-sensitive K+ channel in neuronal membranes. J Biol Chem 260:3895–3898
Tashmoush AJ, Askanas V, Nelson PG, Engel WK (1983) Electrophysiological properties of aneurally cultured muscle from patients with myotonic muscular atrophy. Neurology 33:311–316
Todorov A, Jequier M, Klein D, Morton NE (1970) Analyse de la ségrégation dans la dystrophic myotonique. J Hum Genet 18:387–406
Vincent JP, Schweitz H, Lazdunski M (1975) Structure-function relationships and site of action of apamin. A neurotoxic polypeptide of bee venom with an action on the central nervous system. Biochemistry 14:2521–2525
Wemmer D, Kallenbach NR (1983) Structure of apamin in solution, 2 dimensional NMR study. Biochemistry 22:1901–1906
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Lazdunski, M. et al. (1988). The Apamin-Sensitive Ca2+-Dependent K+ Channel: Molecular Properties, Differentiation, Involvement in Muscle Disease, and Endogeneous Ligands in Mammalian Brain. In: Baker, P.F. (eds) Calcium in Drug Actions. Handbook of Experimental Pharmacology, vol 83. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71806-9_7
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DOI: https://doi.org/10.1007/978-3-642-71806-9_7
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