Abstract
The mechanism by which voltage-gated ion channels respond to changes in membrane polarization during action potential signaling in excitable cells has been the subject of research attention since the original description of voltage-dependent sodium and potassium flux in the squid giant axon. The cloning of ion channel genes and the identification of point mutations associated with channelopathy diseases in muscle and brain has facilitated an electrophysiological approach to the study of ion channels. Experimental approaches to the study of voltage gating have incorporated the use of thiosulfonate reagents to test accessibility, fluorescent probes, and toxins to define domain-specific roles of voltage-sensing S4 segments. Crystallography, structural and homology modeling, and molecular dynamics simulations have added computational approaches to study the relationship of channel structure to function. These approaches have tested models of voltage sensor translocation in response to membrane depolarization and incorporate the role of negative countercharges in the S1 to S3 segments to define our present understanding of the mechanism by which the voltage sensor module dictates gating particle permissiveness in excitable cells.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aggarwal S, MacKinnon R (1996) Contribution of the S4 segment to gating charge in the Shaker K + channel. Neuron 16:1169–1177
Amaral C, Carnevale V, Klein ML, Treptow W (2012) Exploring conformational states of the bacterial sodium channel NaVAb via molecular dynamics simulations. Proc Natl Acad Sci U S A 109:21366–21341
Arcisio-Miranda M, Muroi Y, Chowdhury S, Chanda B (2010) Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics. J Gen Physiol 136:541–554
Armstrong CM (2006) Na channel inactivation from open and closed states. Proc Natl Acad Sci U S A 103:17991–17996
Armstrong CM, Bezanilla F (1973) Currents related to movement of the gating particles of the sodium channels. Nature 242:459–461
Armstrong CM, Bezanilla F (1974) Charge movement associated with the opening and closing of the activation gates of the Na channel. J Gen Physiol 65:533–552
Armstrong CM, Bezanilla F (1977) Inactivation of the sodium channel II. Gating current experiments. J Gen Physiol 70:567–590
Armstrong CM, Hille B (1998) Voltage-gated ion channels and electrical excitability. Neuron 20:371–380
Baker OS, Larsson HP, Mannuzzu M, Isacoff EF (1998) Three transmembrane conformations and sequence-dependent displacement of the S4 domain in Shaker K + channel gating. Neuron 20:1283–1294
Bendahhou S, Cummins T, Kwiecinski H, Waxman S, Ptacek L (1999) Characterization of a new sodium channel mutation at arginine 1448 associated with moderate paramyotonia congenita in humans. J Physiol 518:337–344
Benzinger GR, Kyle JW, Blumenthal KM, Hanck DA (1998) A specific interaction between the cardiac sodium channel and site-3 toxin anthopleurin B. J Biol Chem 273:80–84
Bezanilla F (2008) How membrane proteins sense voltage. Nat Rev 9:323–331
Blanchet J, Chahine M (2007) Accessibility of the four arginine residues on the S4 segment of the Bacillus halodurans sodium channel. J Membr Biol 215:169–180
Blumenthal KM, Seibert AL (2003) Voltage-gated sodium channel toxins. Poisons, probes and future promise. Cell Biochem Biophys 38:215–237
Bosmans F, Swartz KJ (2010) Targeting voltage sensors in sodium channels with spider toxins. Trends Pharmacol Sci 31:175–182
Broomand A, Elinder F (2008) Large-scale movement with the voltage-sensor of a potassium channel-support for a helical-screw motion. Neuron 59:770–777
Campos FV, Beirao PSL (2006) Effects of bound Ts3 on voltage dependence of sodium channel transitions to and from inactivation and energetics of its unbinding. Cell Biochem Biophys 44:424–430
Campos FV, Coronas FIV, Beirao PSL (2004) Voltage-dependent displacement of the scorpion toxin Ts3 from sodium channels and its implication on the control of inactivation. Br J Pharamacol 142:1115–1122
Campos FV, Chanda B, Beirao PSL, Bezanilla F (2007) β-scorpion toxin modifies gating transitions in all four voltage sensors of the sodium channel. J Gen Physiol 130:257–268
Campos FV, Chanda B, Beirao PSL, Bezanilla F (2008) α-scorpion toxin impairs a conformational change that leads to fast inactivation of muscle sodium channels. J Gen Phys 132:251–263
Cannon SC (2006) Pathomechanisms in channelopathies of skeletal muscle and brain. Ann Rev Neurol 29:387–415
Cannon SC (2010) Voltage sensor mutations in channelopathies of skeletal muscle. J Physiol 588:1887–1895
Carle T, Lhuillier L, Luce S, Sternberg D, Devust O, Fonataine B, Tabti N (2006) Gating defects of a novel Na + channel mutant causing hypokalemic periodic paralysis. Biochem Biophys Res Comm 348:653–661
Catterall WA (2010) Ion channel voltage sensors: structure, function and pathophysiology. Neuron 67:915–928
Catterall WA (2012) Voltage gated sodium channels at 60: structure, function and pathophysiology. J Physiol 590:2577–2589
Catterall WA, Beress L (1978) Sea anemone toxin and scorpion toxin share a common receptor site associated with the sodium channel ionophore. J Biol Chem 253:7393–7396
Catterall WA, Cestele S, Yarov-Yarovoy V, Konoki K, Scheuer T (2007) Voltage-gated ion channels and gating modifier toxins. Toxicon 49:124–141
Cestele S, Qu Y, Rogers JC, Bochat H, Scheurer T, Catterall WA (1998) Voltage-sensor trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II. Neuron 1998(21):919–931
Cestele S, Yarov-Yarovoy V, Qu Y, Sampieri F, Scheuer T, Catterall WA (2006) Structure and function of the voltage sensor of sodium channels probed by a b scorpion toxin. J Biol Chem 30:21332–21344
Cha A, Bezanilla F (1997) Characterizing the voltage-dependent conformational changes in the Shaker K + channel with fluorescence. Neuron 19:1127–1140
Cha A, Ruben PC, George AL Jr, Fujimoto E, Bezanilla F (1999) Voltage sensors in domains III and IV, but not I and II, are immobilized by Na + channel fast inactivation. Neuron 22:73–87
Chahine M, George AL Jr, 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
Chakrapani S, Sompornpisut P, Intharathep P, Roux B, Perozo E (2010) The activated state of a sodium channel voltage sensor in a membrane environment. Proc Natl Acad Sci U S A 107:5435–5440
Chanda B, Bezanilla F (2002) Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation. J Gen Physiol 120:629–645
Chanda B, Asamoah OK, Bezanilla F (2004) Coupling interactions between voltage sensors of the sodium channel as revealed by site-specific measurements. J Gen Physiol 123:217–230
Chanda B, Bezanilla F (2008) A common pathway for charge transport through voltage sensing domains. Neuron 57:345–351
Chen J, Mitcheson JS, Lin M, Sanguinetti MC (2000) Functional roles of charged residues in the putative voltage sensor of the HCN2 pacemaker channel. J Biol Chem 275:36465–36471
Chen L-Q, Santarelli V, Horn R, Kallen RG (1996) A unique role for the S4 segment of domain 4 in the inactivation of sodium channels. J Gen Physiol 108:549–556
Clayton GM, Altieri S, Heginbotham L, Unger VM, Morais-Cabral JH (2008) Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel. Proc Natl Acad Sci U S A 105:1511–1515
Cole KS, Curtis HJ (1938) Electrical impedance of Nitella during activity. J Gen Physiol 22:37–64
Cole KS, Curtis HJ (1939) Electrical impedance of the squid giant axon during activity. J Gen Physiol 22:649–670
Cuello LG, Cortes DM, Perozo E (2004) Molecular architecture of the KVAP voltage-dependent K + channel in a lipid bilayer. Science 306:491–495
DeCaen PG, Yarov-Yarovoy V, Zhao Y, Scheurer T, Catterall WA (2008) Disulfide locking of a sodium channel voltage sensor reveals ion pair formation during activation. Proc Natl Acad Sci U S A 105:15142–15147
DeCaen PG, Yarov-Yarovoy V, Sharp EM, Scheurer T, Catterall WA (2009) Sequential formation of ion pairs during activation of a sodium channel voltage sensor. Proc Natl Acad Sci U S A 106:22498–22503
DeCaen PG, Yarov-Yarovoy V, Scheurer T, Catterall WA (2011) Gating charge interactions with the S1 segment during activation of a Na + channel voltage sensor. Proc Natl Acad Sci U S A 108:18825–18830
Delemotte L, Treptow W, Klein ML, Tarek M (2010) Effect of sensor domain mutations on the properties of voltage-gated ion channels: molecular dynamics studies of the potassium channel KV1.2. Biophys J 99:L72–L74
Delemotte L, Tarek M, Klein ML, Amaral C, Treptow W (2011) Intermediate states of the KV1.2 voltage sensor from atomistic molecular dynamics simulations. Proc Natl Acad Sci U S A 108:6109–6114
Delemotte L, Klein ML, Tarek M (2012) Molecular dynamics simulations of voltage-gated cation channels: insights on voltage-sensor domain function and modulation. Front Pharmacol 3:1–15
Du Y, Song W, Groome JR, Nomura Y, Luo N, Dong K (2010) A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides. Toxicol Appl Pharmacol 247:53–59
Doyle DA, Cabral JM, Pfuetnzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1988) The structure of the potassium channel: molecular basis of K + conduction and selectivity. Science 280:69–77
Dror RO, Jensen MO, Borhani DW, Shaw DE (2010) Exploring atomic resolution on a femtosecond to millisecond timescale using molecular dynamics simulations. J Gen Physiol 135:555–562
Eldstrom J, Xu H, Werry D, Kang C, Loewen ME, Degenhardt A, Sanatani S, Tibbits GF, Sanders C, Fedida D (2010) Mechanistic basis for LQT1 caused by S3 mutations in the KCNQ1 subunit of IKs. J Gen Physiol 135:433–438
El-Sharif N, Fozzard HA, Hanck DA (1992) Dose-dependent modulation of the cardiac sodium channel by sea anemone toxin ATXII. Circ Res 70:285–301
Filatov GN, Nguyen TP, Kraner SD, Barchi RL (1998) Inactivation and secondary structure in the D4/S4-5 region of the SkM1 sodium channel. J Gen Physiol 111:703–715
Francis DG, Rybalchenko V, Struyk A, Cannon SC (2011) Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not myotonia. Neurology 76:1–7
Gajewski C, Dagcan A, Roux B, Deutsch C (2011) Biogenesis of the pore architecture of a voltage-gated potassium channel. Proc Natl Acad Sci U S A 108:3240–3245
George AL Jr (2012) Leaky channels make weak muscles. J Clin Invest 122:4333–4326
Gosselin-Badaroudine P, Keller D, Huang H, Pouliot V, Chatelier A, Osswald S, Brink M, Chahine M (2012a) A proton leak current through the cardiac sodium channel is linked to mixed arrhythmia and the dilated cardiomyopathy phenotype. PLoS One 7:1–11
Gosselin-Badaroudine P, Delemotte L, Moreau A, Klein ML, Chahine M (2012b) Gating pore currents and the resting state of NaV1.4 voltage sensor domains. Proc Natl Acad Sci U S A 109:19250–19255
Groome JR, Winston V (2013) S1-S3 counter charges in the voltage sensor module of a mammalian sodium channel regulate fast inactivation. J Gen Phys 141:601–618
Groome JR, Fujimoto E, George AL Jr, Ruben PC (1999) Differential effects of homologous S4 mutations in human skeletal muscle sodium channels on deactivation gating from open and inactivated states. J Physiol 516:687–698
Groome JR, Fujimoto E, Walter L, Ruben P (2002) Outer and central charged residues in DIVS4 of skeletal muscle sodium channels have differing roles in deactivation. Biophys J 82:1293–1307
Groome JR, Holzherr BD, Lehmann-Horn F (2011) Open- and closed-state fast inactivation in sodium channels. Differential effects of a site-3 anemone toxin. Channels 5:1–14
Gur M, Kahn R, Karbat I, Regev N, Wang J, Catterall WA, Gordon D, Gurevitz M (2011) Elucidation of the molecular basis of selective recognition uncovers the interaction site for the core domain of scorpion α-toxins on sodium channels. J Biol Chem 286:35209–35217
Guy HR, Seetharamulu P (1986) Molecular model of the action potential sodium channel. Proc Natl Acad Sci U S A 83:508–512
Hanck DA, Sheets MF (1995) Modification of inactivation in cardiac sodium channels: ionic current studies with anthopleurin-A toxin. J Gen Physiol 106:601–616
Hanck DA, Sheets MF (2007) Site-3 toxins and cardiac sodium channels. Toxicon 49:181–193
Henrion U, Renhorn J, Borjesson SI, Neslon SI, Nelson EM, Schwaiger CS, Bjelkmar P, Wallner B, Lindhal E, Elinder F (2012) Tracking a complete voltage sensor with metal-ion bridges. Proc Natl Acad Sci U S A 109:8552–8557
Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500–544
Holzherr, BD, Groome JR, Fauler M, Nied E, Lehmann-Horn F, Jurkat-Rott K (2010) Characterization of a novel hNaV1.4 mutation causing hypokalemic periodic paralysis. Biophys Soc Abstr LB201
Horn R, Ding S, Gruber HJ (2000) Immobilizing the moving parts of voltage-gated ion channels. J Gen Physiol 116:461–475
Horne AJ, Peters CJ, Claydon TW, Fedida D (2010) Fast and slow voltage sensor rearrangements during activation gating in Kv1.2 channels detected using tetramethylrhodamine fluorescence. J Gen Physiol 136:83–99
Jensen MO, Borhani DW, Lindorff-Laren K, Maragakis P, Jogini V, Eastwood MP, Dror RO, Shaw DE (2010) Principles of conduction and hydrophobic gating in K + channels. Proc Natl Acad Sci U S A 107:5833–5838
Jensen MO, Jogini V, Borhani DW, Leffler AE, Dror RO, Shaw DE (2012) Mechanism of voltage gating in potassium channels. Science 336:229–233
Jensen MO, Jogini V, Eastwood MP, Shaw DE (2013) Atomic-level simulation of current-voltage relationships in single-file ion channels. J Gen Physiol 141:619–632
Jiang Y, Lee A, Ruta V, Cadene M, Chait BT, MacKinnon R (2003) X-ray structure of a voltage-dependent K + channel. Nature 423:33–41
Jiang Q-X, Wang D-N, MacKinnon R (2004) Electron microscopic analysis of KVAP voltage-dependent K + channels in an open conformation. Nature 430:806–810
Jogini V, Roux B (2007) Dynamics of the KV1.2 voltage-gated K+ channel in a membrane environment. Biophys J 93:3070–3082
Jover E, Couraud F, Rochat H (1980) Two types of scorpion neurotoxins characterized by their binding to two separate receptor sites on rat brain synaptosomes. Biocim Biophys Res Commun 95:1607–1614
Jurkat-Rott K, Mitrovic N, Hang C, Kouzmekine A, Iaizzo P, Herzog J, Lerche H, Nicole S, Vale-Santos S, Chauveau D, Fontaine B, Lehmann-Horn F (2000) Voltage sensor mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proc Natl Acad Sci U S A 97:9549–9554
Jurkat-Rott K, Holzherr B, Fauler M, Lehmann-Horn F (2010) Sodium channelopaties of skeletal muscle result from gain or loss of function. Plugers Arch 460:239–248
Jurkat-Rott K, Groome JR, Lehmann-Horn F (2012) Pathophysiological role of omega pore current in channelopathies. Front Neuropharmacol 3:1–15
Kahn R, Karbat I, Ilan N, Cohen L, Sokolov S, Catterall WA, Gordon D, Gurevitz M (2009) Molecular requirements for recognition of brain voltage-gated sodium channels by scorpion a-toxins. J Biol Chem 284:20684–20691
Kambouris NG, Nuss HB, Johns DC, Tomaselli GF, Marban E, Balser JR (1998) Phenotypic characterization of a novel long-QT syndrome mutation (R1623Q) in the cardiac sodium channel. Circulation 97:640–644
Kambouris NG, Nuss HB, Johns DC, Marban E, Tomaselli GF, Balser JR (2000) A revised view of cardiac sodium channel “blockade” in the long QT syndrome. J Clin Invest 105:1133–1140
Khalili-Araghi F, Tajkhorsid E, Roux B, Schulten K (2012) Molecular dynamics investigation of the w-current in the KV1.2 voltage sensor domains. Biophys J 102:258–267
Kontis KJ, Goldin AL Jr (1997) Sodium channel inactivation is altered by substitution of voltage sensor positive charges. J Gen Physiol 110:403–413
Kontis KJ, Rounaghi A, Goldin AL Jr (1997) Sodium channel activation gating is affected by substitutions of voltage sensor positive charges in all four domains. J Gen Physiol 110:391–401
Kuzmenkin A, Muncan V, Jurkat-Rott K, Hang C, Lerche H, Lehmann-Horn F, Mitrovic N (2002) Enhanced inactivation and pH sensitivity of Na + channel mutations causing hypokalemic periodic paralysis type II. Brain 125:825–843
Lacroix J, Pless SA, Maragliano L, Campos FV, Galpin JD, Ahern CA, Roux B, Bezanilla F (2012) Intermediate state trapping of a voltage sensor. J Gen Physiol 140:635–652
Lee S-Y, Lee A, Chen J, MacKinnon R (2005) Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane. Proc Natl Acad Sci USA 102:15441–15446
Leipold E, Borges A, Heinemann SH (2012) Scorpion β-toxin interference with NaV channel voltage sensor gives rise to excitatory and depressant modes. J Gen Physiol 139:305–319
Lerche H, Mitrovic N, Dubowitz V, Lehmann-Horn F (1996) Paramyotonia congenita: the R1448P Na + channel mutation in adult human skeletal muscle. Ann Neurol 39:599–608
Lerche H, Peter W, Fleischhauer R, Pika-Hartlaub U, Malina T, Mitrovic N, Lehmann-Horn F (1997) Role in fast inactivation of the IV/S4-S5 loop of the human muscle Na + channel probed by cysteine mutagenesis. J Physiol 505:345–352
Lin M-C, Hsieh J-Y, Mock AF, Papapzian DM (2011) R1 in the Shaker S4 occupies the gating charge transfer center in the resting state. J Gen Physiol 138:155–163
Long SB, Campbell EB, MacKinnon R (2005a) Crystal structure of a mammalian voltage-dependent Shaker K + channel. Science 309:897–903
Long SB, Campbell EB, MacKinnon R (2005b) Voltage sensor of KV1.2: structural basis of electromechanical coupling. Science 309:903–908
Long SB, Tao X, Campbell EB, MacKinnon R (2007) Atomic structure of a voltage-dependent K + channel in a lipid membrane-like environment. Nature 450:376–382
Ma Z, Lou XJ, Horrigan FT (2006) Role of charged residues in the S1-S4 voltage sensor of BK channels. J Gen Physiol 127:309–328
McPhee JC, Ragsdale DS, Scheuer T, Catterall WA (1998) A critical role for the S4-S5 intracellular loop in domain IV of the sodium channel a subunit in fast inactivation. J Biol Chem 273:1121–1129
Mitrovic N, Lerche H, Heine R, Fleischhauer R, Pika-Hartlaub U, Hartlaub U, George AL Jr, Lehmann-Horn F (1996) Role in fast inactivation of conserved amino acids in the IV/S4-S5 loop of the human muscle Na + channel. Neurosci Lett 214:9–12
Mohammadi B, Mitrovic N, Lehmann-Horn F, Dengler R, Bufler J (2003) Mechanisms of cold sensitivity of paramyotonia congenita mutation R1448H and overlap syndrome mutation M1360V. J Physiol 547:691–698
Mohammadi B, Jurkat-Rott K, Alekov A, Dengler R, Bufler J, Lehmann-Horn F (2005) Preferred mexiletine block of human sodium channels with IVS4 mutations and its pH dependence. Pharm Genomics 15:235–244
Montegazza M, Cestele S (2005) β-scorpion toxin effects suggest electrostatic interaction in domain II of voltage-dependent sodium channels. J Physiol 568:13–30
Moran Y, Gordon D, Gurevitz M (2009) Sea anemone toxins affecting voltage-gated sodium channels: molecular and evolutionary features. Toxicon 54:1089–1101
Muroi Y, Chanda B (2008) Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel. J Gen Physiol 133:1–15
Muroi Y, Arcisio-Miranda M, Chowdhury S, Chanda B (2010) Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel. Nat Struct Mol Biol 17:230–237
Neumcke B, Schwarz W, Stampfl R (1985) Comparison of the effects of Anemonia toxin II on sodium and gating currents in frog myelinated nerve. Biochim Biophys Acta 814:111–119
Noda MS, Shizimu S, Tanabe T, Takai T, Kayano T, Ikeda T, Takahashi H, Nakayami Y, Kamaoka N, Minamino N, Kangawa K, Matsuo K, Raferty H, Hirose M, Inayama T, Hayashida H, Miyata T, Numa S (1984) Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312:121–127
Paldi T, Gurevitz M (2010) Coupling between residues on S4 and S1 defines the voltage-sensor resting conformation in NaChBac. Biophys J 99:456–463
Pan AC, Cuello LG, Perozo E, Roux B (2011) Thermodynamic coupling between activation and inactivation gating in potassium channels reveled by free energy molecular dynamics simulations. J Gen Physiol 138:571–580
Papazian DM, Shao XM, Seoh S-A, Mock AF, Huang Y, Wainstock DH (1995) Electrostatic interactions of S4 voltage sensor in Shaker K+ channel. Neuron 14:1–20
Pathak MM, Yarovy-Yarovy V, Agarwal G, Roux B, Barth P, Kohout S, Tombola F, Iscaof EY (2007) Closing in on the resting state of the Shaker (K+) channel. Neuron 56:124–140
Payandeh J, Scheurer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature 475:353–358
Payandeh J, El-Din G, Scheuer T, Zheng N, Catterall WA (2012) Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. Nature 486:135–140
Pless SA, Galpin JD, Niciforovic AP, Ahern CA (2011) Contributions of countercharge in a potassium channel voltage-sensor domain. Nat Chem Biol 7:617–623
Possani LD, Becerril B, Delepierre M, Tytgat J (1999) Scorpion toxins specific for Na + -channels. Eur Biochem 264:287–300
Richmond JE, Featherstone DE, Ruben PC (1997) Human Na + channel fast and slow inactivation in paramyotonia congenita mutants expressed in Xenopus laevis oocytes. J Physiol 499:589–600
Rogers JC, Qu Y, Tanada TN, Scheuer T, Catterall WA (1996) Molecular determinants of high affinity binding of a-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na + channel a subunit. J Biol Chem 271:15950–15962
Roux B (2010) Perspectives on: molecular dynamics and computational methods. J Gen Physiol 135:547–548
Schwaiger CS, Bjelkmar P, Hess B, Lindhal E (2011) 3-10 helix conformation facilitates the transition of a voltage sensor S4 segment toward the down state. Biophys J 100:1446–1454
Seoh S-A, Sigg D, Papazian DM, Bezanilla F (1996) Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel. Neuron 16:1159–1167
Shafrir Y, Durell SR, Guy HR (2008) Models of voltage-dependent conformational changes in NaChBac channels. Biophys J 95:3663–3676
Sheets MF, Hanck DA (1995) Voltage-dependent open-state inactivation of cardiac sodium channels: gating current studies with anthopleurin-A toxin. J Gen Physiol 106:617–640
Sheets MF, Hanck DA (2002) The outermost lysine of domain III contributes little to the gating charge in sodium channels. Biophys J 82:348–3055
Sheets MF, Hanck DA (2005) Charge immobilization of the voltage sensor in domain IV is independent of sodium current inactivation. J Physiol 563:89–93
Sheets MF, Kyle JW, Kallen RG, Hanck DA (1999) The Na channel voltage sensor associated with fast inactivation is localized to the external charged residues of domain IV, S4. Biophys J 77:747–757
Sheets MF, Kyle JW, Hanck DA (2000) The role of the putative inactivation lid in sodium channel gating. J Gen Physiol 115:609–619
Sigworth F (2007) The last few frames of the voltage-gating movie. Biophys J 93:2981–2983
Silverman WR, Roux B, Papazian DM (2003) Structural basis of two-stage voltage-dependent activation in K + channels. Proc Natl Acad Sci U S A 100:2935–2940
Sokolov S, Scheuer T, Catterall WA (2005) Ion permeation through a voltage-sensitive gating pore in brain sodium channels having voltage sensor mutations. Neuron 47:183–189
Sokolov S, Scheuer T, Catterall WA (2008a) Depolarization-activated gating pore current conducted by mutant sodium channels in potassium-sensitive normokalemic periodic paralysis. Proc Natl Acad Sci 105:19980–19985
Sokolov S, Kraus RL, Scheuer T, Catterall WA (2008b) Inhibition of sodium channel gating by trapping the domain II voltage sensor with protoxin II. Mol Pharmacol 73:1020–1028
Sokolov S, Scheurer T, Catterall WA (2010) Ion permeation and block of the gating pore in the voltage sensor of NaV1.4 channels with hypokalemic periodic paralysis mutations. J Gen Physiol 136:225–236
Sompornpisut P, Roux B, Perozo E (2008) Structural refinement of membrane proteins by restrained molecular dynamics and solvent accessibility data. Biophys J 95:5349–5361
Song W, Du Y, Liu Z, Luo N, Turkov M, Gordon D, Gurevitz M, Goldin A, Dong K (2011) Substitutions in the domain III voltage-sensing module enhance the sensitivity of an insect sodium channel to a scorpion β-toxin. J Biol Chem 286:15781–15788
Starace DM, Bezanilla F (2004) A proton pore in a potassium channel reveals a focused electric field. Nature 427:548–553
Struyk AF, Cannon SC (2007) A Na + channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore. J Gen Physiol 130:11–20
Struyk AF, Scoggan KA, Bulman DE, Cannon SC (2000) The human skeletal muscle Na channel mutation R669H associated with hypokalemic periodic paralysis enhances slow inactivation. J Neurosci 20:8610–8617
Struyk AF, Markin VS, Francis D, Cannon SC (2008) Gating pore currents in DIIS4 mutations of NaV1.4 associated with periodic paralysis: saturation of ion flux and implications for disease pathogenesis. J Gen Physiol 132:447–464
Stuhmer W, Conti F, Suzuki H, Wang X, Noda N, Yahagi N, Kubo H, Numa S (1989) Structural parts involved in activation and inactivation of the sodium channel. Nature 339:597–604
Tang L, Kallen RG, Horn R (1996) Role of an S4-S5 linker in sodium channel inactivation probed by mutagenesis and a peptide blocker. J Gen Physiol 108:89–104
Tombola F, Pathak MM, Isacoff EY (2005) Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores. Neuron 45:379–388
Treptow W, Tarek M, Klein ML (2009) Initial response of the potassium channel voltage sensor to a transmembrane potential. J Am Chem Soc 131:2107–2109
Vargas E, Yarov-Yarovoy V, Khalili-Araghi F, Catterall WA, Klein ML, Tarek M, Lindhal E, Schulten K, Perozo E, Bezanilla F, Roux B (2012) An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations. J Gen Physiol 140:587–594
Wang J, Yarov-Yarovoy V, Kahn R, Gordon D, Gurevitz M, Scheuer T, Catterall WA (2011) Mapping the receptor site for a-scorpion toxins on an Na + channel voltage sensor. Proc Natl Acad Sci U S A 108:15426–15431
Yang N, Horn R (1995) Evidence for voltage-dependent S4 movement in sodium channels. Neuron 15:213–218
Yang N, Ji S, Zhou M, Ptacek 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 U S A 91:12785–12789
Yang N, George AL Jr, Horn R (1996) Molecular basis of charge movement in voltage-gated sodium channels. Neuron 16:113–122
Yarov-Yarovoy V, Baker D, Catterall WA (2006) Voltage sensor conformations in the open and closed states in ROSETTA structural models of K (+) channels. Proc Natl Acad Sci U S A 103:7292–7297
Yarov-Yarovoy V, DeCaen PG, Westenbroek RE, Pan C-Y, Scheuer T, Baker D, Catterall WA (2012) Structural basis for gating charge movement in the voltage sensor of a sodium channel. Proc Natl Acad Sci U S A 109:E93–E102
Yu FH, Yarov-Yarovoy V, Gutman GA, Catterall WA (2005) Overview of molecular relationships in the voltage-gated ion channel superfamily. Phys Rev 57:387–395
Zhang JZ, Yarov-Yarovoy V, Scheuer T, Karbat I, Cohen L, Gordon D, Gurevitz M, Catterall WA (2011) Structure-function map of the receptor site for b-scorpion toxins in domain II of voltage-gated sodium channels. J Biol Chem 286:33641–33651
Zhang X, Ren W, DeCaen P, Yan C, Tao X, Tang L, Wang J, Hasegawa K, Kumasaka T, He J, Wang J, Clapham DE, Yan N (2012) Crystal structure of an orthologue of NachBac voltage-gated sodium channel. Nature 486:130–134
Zuo X-P, Ji Y-H (2004) Molecular mechanism of scorpion neurotoxins acting on sodium channels. Insight into their diverse selectivity. Mol Neurobiol 30:265–278
Acknowledgments
This work was supported by NIH 1R15NSO64556-01 to JRG and by NIH P20 RR016454 to Idaho State University. Thanks are given to V Winston (Biology Department, ISU) for contribution of homology models for hNaV1.4 and molecular dynamics simulations. This work is dedicated to the memory of the late Esther Fujimoto.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Groome, J.R. (2014). The Voltage Sensor Module in Sodium Channels. In: Ruben, P. (eds) Voltage Gated Sodium Channels. Handbook of Experimental Pharmacology, vol 221. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-41588-3_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-41588-3_2
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-41587-6
Online ISBN: 978-3-642-41588-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)