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Mechanisms of Drug Binding to Voltage-Gated Sodium Channels

  • M. E. O’Leary
  • M. Chahine
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 246)

Abstract

Voltage-gated sodium (Na+) channels are expressed in virtually all electrically excitable tissues and are essential for muscle contraction and the conduction of impulses within the peripheral and central nervous systems. Genetic disorders that disrupt the function of these channels produce an array of Na+ channelopathies resulting in neuronal impairment, chronic pain, neuromuscular pathologies, and cardiac arrhythmias. Because of their importance to the conduction of electrical signals, Na+ channels are the target of a wide variety of local anesthetic, antiarrhythmic, anticonvulsant, and antidepressant drugs. The voltage-gated family of Na+ channels is composed of α-subunits that encode for the voltage sensor domains and the Na+-selective permeation pore. In vivo, Na+ channel α-subunits are associated with one or more accessory β-subunits (β1–β4) that regulate gating properties, trafficking, and cell-surface expression of the channels. The permeation pore of Na+ channels is divided in two parts: the outer mouth of the pore is the site of the ion selectivity filter, while the inner cytoplasmic pore serves as the channel activation gate. The cytoplasmic lining of the permeation pore is formed by the S6 segments that include highly conserved aromatic amino acids important for drug binding. These residues are believed to undergo voltage-dependent conformational changes that alter drug binding as the channels cycle through the closed, open, and inactivated states. The purpose of this chapter is to broadly review the mechanisms of Na+ channel gating and the models used to describe drug binding and Na+ channel inhibition.

Keywords

Gating Local anesthetics Nav Sodium channels Structure-function 

References

  1. Ahern CA, Eastwood AL, Dougherty DA, Horn R (2008) Electrostatic contributions of aromatic residues in the local anesthetic receptor of voltage-gated sodium channels. Circ Res 102:86–94PubMedCrossRefGoogle Scholar
  2. Akopian AN, Souslova V, Sivilotti L, Wood JN (1997) Structure and distribution of a broadly expressed atypical sodium channel. FEBS Lett 400:183–187PubMedCrossRefGoogle Scholar
  3. Aldrich RW, Corey DP, Stevens CF (1983) A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature 306:436–441PubMedCrossRefGoogle Scholar
  4. Armstrong CM (1966) Time course of TEA(+)-induced anomalous rectification in squid giant axons. J Gen Physiol 50:491–503PubMedPubMedCentralCrossRefGoogle Scholar
  5. Armstrong CM (1971) Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol 58:413–437PubMedPubMedCentralCrossRefGoogle Scholar
  6. Armstrong CM, Bezanilla F (1973) Currents related to movement of the gating particles of the sodium channels. Nature 242:459–461PubMedCrossRefGoogle Scholar
  7. Armstrong CM, Bezanilla F (1977) Inactivation of the sodium channel. II. Gating current experiments. J Gen Physiol 70:567–590PubMedCrossRefGoogle Scholar
  8. Armstrong CM, Bezanilla F, Rojas E (1973) Destruction of sodium conductance inactivation in squid axons perfused with pronase. J Gen Physiol 62:375–391PubMedPubMedCentralCrossRefGoogle Scholar
  9. 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 257:248–251PubMedCrossRefGoogle Scholar
  10. Bagneris C, DeCaen PG, Hall BA, Naylor CE, Clapham DE, Kay CW, Wallace BA (2013) Role of the C-terminal domain in the structure and function of tetrameric sodium channels. Nat Commun 4:2465PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bagneris C, DeCaen PG, Naylor CE, Pryde DC, Nobeli I, Clapham DE, Wallace BA (2014) Prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism. Proc Natl Acad Sci U S A 111:8428–8433PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bagneris C, Naylor CE, McCusker EC, Wallace BA (2015) Structural model of the open-closed-inactivated cycle of prokaryotic voltage-gated sodium channels. J Gen Physiol 145:5–16PubMedPubMedCentralCrossRefGoogle Scholar
  13. Balser JR, Nuss HB, Romashko DN, Marban E, Tomaselli GF (1996) Functional consequences of lidocaine binding to slow-inactivated sodium channels. J Gen Physiol 107:643–658PubMedCrossRefGoogle Scholar
  14. Baroudi G, Napolitano C, Priori SG, Del BA, Chahine M (2004) Loss of function associated with novel mutations of the SCN5A gene in patients with Brugada syndrome. Can J Cardiol 20:425–430PubMedGoogle Scholar
  15. Baukrowitz T, Yellen G (1996) Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel. Science 271:653–656PubMedCrossRefGoogle Scholar
  16. Bean BP, Cohen CJ, Tsien RW (1983) Lidocaine block of cardiac sodium channels. J Gen Physiol 81:613–642PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bennett PB, Valenzuela C, Chen LQ, Kallen RG (1995a) On the molecular nature of the lidocaine receptor of cardiac Na+ channels. Modification of block by alterations in the alpha-subunit III-IV interdomain. Circ Res 77:584–592PubMedCrossRefGoogle Scholar
  18. Bennett PB, Yazawa K, Makita N, George AL Jr (1995b) Molecular mechanism for an inherited cardiac arrhythmia. Nature 376:683–685PubMedCrossRefGoogle Scholar
  19. Brackenbury WJ, Djamgoz MB, Isom LL (2008) An emerging role for voltage-gated Na channels in cellular migration: regulation of central nervous system development and potentiation of invasive cancers. Neurosci 14:571–583Google Scholar
  20. Brugada P, Brugada J (1992) Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 20:1391–1396PubMedCrossRefGoogle Scholar
  21. Butterworth JF, Strichartz GR (1990) Molecular mechanisms of local anesthesia: a review. Anesthesiology 72:711–734PubMedCrossRefGoogle Scholar
  22. Cahalan MD (1978) Local anesthetic block of sodium channels in normal and pronase-treated squid giant axons. Biophys J 23:285–311PubMedPubMedCentralCrossRefGoogle Scholar
  23. Cahalan MD, Almers W (1979a) Block of sodium conductance and gating current in squid giant axons poisoned with quaternary strychnine. Biophys J 27:57–73PubMedPubMedCentralCrossRefGoogle Scholar
  24. Cahalan MD, Almers W (1979b) Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin. Biophys J 27:39–55PubMedPubMedCentralCrossRefGoogle Scholar
  25. Capes DL, Goldschen-Ohm MP, Arcisio-Miranda M, Bezanilla F, Chanda B (2013) Domain IV voltage-sensor movement is both sufficient and rate limiting for fast inactivation in sodium channels. J Gen Physiol 142:101–112PubMedPubMedCentralCrossRefGoogle Scholar
  26. Catterall WA (1986) Molecular properties of voltage-sensitive sodium channels. Annu Rev Biochem 55:953–985PubMedCrossRefGoogle Scholar
  27. Catterall WA (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26:13–25PubMedCrossRefGoogle Scholar
  28. Catterall WA (2014) Structure and function of voltage-gated sodium channels at atomic resolution. Exp Physiol 99:35–51PubMedCrossRefGoogle Scholar
  29. Catterall WA, Goldin AL, Waxman SG (2005) International union of pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57:397–409PubMedCrossRefGoogle Scholar
  30. 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 22:73–87PubMedCrossRefGoogle Scholar
  31. Chahine M, O’Leary ME (2014) Regulation/modulation of sensory neuron sodium channels. Handb Exp Pharmacol 221:111–135PubMedCrossRefGoogle Scholar
  32. 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 12:281–294PubMedCrossRefGoogle Scholar
  33. Chahine M, Deschenes I, Trottier E, Chen LQ, Kallen RG (1997) Restoration of fast inactivation in an inactivation-defective human heart sodium channel by the cysteine modifying reagent benzyl-MTS: analysis of IFM-ICM mutation. Biochem Biophys Res Commun 233:606–610PubMedCrossRefGoogle Scholar
  34. Chahine M, Chatelier A, Babich O, Krupp JJ (2008) Voltage-gated sodium channels in neurological disorders. CNS Neurol Disord Drug Targets 7:144–158PubMedCrossRefGoogle Scholar
  35. Chanda B, Bezanilla F (2002) Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation. J Gen Physiol 120:629–645PubMedPubMedCentralCrossRefGoogle Scholar
  36. Chen LQ, 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 108:549–556PubMedCrossRefGoogle Scholar
  37. Chen Z, Ong BH, Kambouris NG, Marban E, Tomaselli GF, Balser JR (2000) Lidocaine induces a slow inactivated state in rat skeletal muscle sodium channels. J Physiol 524:37–49PubMedPubMedCentralCrossRefGoogle Scholar
  38. Corry B, Lee S, Ahern CA (2014) Pharmacological insights and quirks of bacterial sodium channels. Handb Exp Pharmacol 221:251–267PubMedCrossRefGoogle Scholar
  39. Courtney KR (1975) Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA. J Pharmacol Exp Ther 195:225–236PubMedGoogle Scholar
  40. Courtney KR (1979) Extracellular PH selectively modulates recovery from sodium inactivation in frog myelinated nerve. Biophys J 28:363–368PubMedPubMedCentralCrossRefGoogle Scholar
  41. Courtney KR, Etter EF (1983) Modulated anticonvulsant block of sodium channels in nerve and muscle. Eur J Pharmacol 88:1–9PubMedCrossRefGoogle Scholar
  42. Dib-Hajj SD, Binshtok AM, Cummins TR, Jarvis MF, Samad T, Zimmermann K (2009) Voltage-gated sodium channels in pain states: role in pathophysiology and targets for treatment. Brain Res Rev 60:65–83PubMedCrossRefGoogle Scholar
  43. Doyle DA, Morais CJ, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:69–77PubMedCrossRefGoogle Scholar
  44. Faraldo-Gomez JD, Kutluay E, Jogini V, Zhao Y, Heginbotham L, Roux B (2007) Mechanism of intracellular block of the KcsA K+ channel by tetrabutylammonium: insights from X-ray crystallography, electrophysiology and replica-exchange molecular dynamics simulations. J Mol Biol 365:649–662PubMedCrossRefGoogle Scholar
  45. Fontaine B, Khurana TS, Hoffman EP, Bruns GA, Haines JL, Trofatter JA, Hanson MP, Rich J, McFarlane H, Yasek DM et al (1990) Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene. Science 250:1000–1002PubMedCrossRefGoogle Scholar
  46. Fozzard HA, Hanck DA (1996) Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms. Physiol Rev 76:887–926PubMedCrossRefGoogle Scholar
  47. Fozzard HA, Lee PJ, Lipkind GM (2005) Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr Pharm Des 11:2671–2686PubMedCrossRefGoogle Scholar
  48. Gingrich KJ, Beardsley D, Yue DT (1993) Ultra-deep blockade of Na+ channels by a quaternary ammonium ion: catalysis by a transition-intermediate state? J Physiol 471:319–341PubMedPubMedCentralCrossRefGoogle Scholar
  49. Goldin AL (2001) Resurgence of sodium channel research. Annu Rev Physiol 63:871–894PubMedCrossRefGoogle Scholar
  50. Goldin AL, Barchi RL, Caldwell JH, Hofmann F, Howe JR, Hunter JC, Kallen RG, Mandel G, Meisler MH, Netter YB, Noda M, Tamkun MM, Waxman SG, Wood JN, Catterall WA (2000) Nomenclature of voltage-gated sodium channels. Neuron 28:365–368PubMedCrossRefGoogle Scholar
  51. Grant AO, Strauss LJ, Wallace AG, Strauss HC (1980) The influence of PH on Th electrophysiological effects of lidocaine in guinea pig ventricular myocardium. Circ Res 47:542–550PubMedCrossRefGoogle Scholar
  52. Grant AO, Trantham JL, Brown KK, Strauss HC (1982) PH-dependent effects of quinidine on the kinetics of DV/Dtmax in guinea pig ventricular myocardium. Circ Res 50:210–217PubMedCrossRefGoogle Scholar
  53. Habbout K, Poulin H, Rivier F, Giuliano S, Sternberg D, Fontaine B, Eymard B, Morales RJ, Echenne B, King L, Hanna MG, Mannikko R, Chahine M, Nicole S, Bendahhou S (2016) A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis. Neurology 86:161–169PubMedPubMedCentralCrossRefGoogle Scholar
  54. Hanck DA, Makielski JC, Sheets MF (2000) Lidocaine alters activation gating of cardiac Na channels. Pflugers Arch 439:814–821PubMedCrossRefGoogle Scholar
  55. Hartmann HA, Colom LV, Sutherland ML, Noebels JL (1999) Selective localization of cardiac SCN5A sodium channels in limbic regions of rat brain. Nat Neurosci 2:593–595PubMedCrossRefGoogle Scholar
  56. Heinemann SH, Terlau H, Stuhmer W, Imoto K, Numa S (1992) Calcium channel characteristics conferred on the sodium channel by single mutations. Nature 356:441–443PubMedCrossRefGoogle Scholar
  57. Hille B (1977) Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515PubMedCrossRefGoogle Scholar
  58. Hille B (2001) Ion channels in excitable membranes. Sinauer, SunderlandGoogle Scholar
  59. Hirschberg B, Rovner A, Lieberman M, Patlak J (1995) Transfer of twelve charges is needed to open skeletal muscle Na+ channels. J Gen Physiol 106:1053–1068PubMedCrossRefGoogle Scholar
  60. Ho C, O’Leary ME (2011) Single-cell analysis of sodium channel expression in dorsal root ganglion neurons. Mol Cell Neurosci 46:159–166PubMedCrossRefGoogle Scholar
  61. Isom LL (2001) Sodium channel beta subunits: anything but auxiliary. Neurosci 7:42–54Google Scholar
  62. Isom LL (2002) b-subunits: players in neuronal hyperexcitability? Novartis Found Symp 241:124–138PubMedGoogle Scholar
  63. Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R (2002) The open pore conformation of potassium channels. Nature 417:523–526PubMedCrossRefGoogle Scholar
  64. Jo S, Bean BP (2017) Lacosamide inhibition of Nav1.7 voltage-gated sodium channels: slow binding to fast-inactivated states. Mol Pharmacol 91:277–286PubMedPubMedCentralCrossRefGoogle Scholar
  65. Jogini V, Roux B (2005) Electrostatics of the intracellular vestibule of K+ channels. J Mol Biol 354:272–288PubMedCrossRefGoogle Scholar
  66. Karoly R, Lenkey N, Juhasz AO, Vizi ES, Mike A (2010) Fast- or slow-inactivated state preference of Na+ channel inhibitors: a simulation and experimental study. PLoS Comput Biol 6:e1000818PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kellenberger S, Scheuer T, Catterall WA (1996) Movement of the Na+ channel inactivation gate during inactivation. J Biol Chem 271:30971–30979PubMedCrossRefGoogle Scholar
  68. Keller DI, Acharfi S, Delacretaz E, Benammar N, Rotter M, Pfammatter JP, Fressart V, Guicheney P, Chahine M (2003) A novel mutation in SCN5A, DelQKP 1507-1509, causing long QT syndrome: role of Q1507 residue in sodium channel inactivation. J Mol Cell Cardiol 35:1513–1521PubMedCrossRefGoogle Scholar
  69. Keynes RD, Rojas E (1974) Kinetics and steady-state properties of the charged system controlling sodium conductance in the squid giant axon. J Physiol 239:393–434PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kimbrough JT, Gingrich KJ (2000) Quaternary ammonium block of mutant Na+ channels lacking inactivation: features of a transition-intermediate mechanism. J Physiol 529:93–106PubMedPubMedCentralCrossRefGoogle Scholar
  71. Lampert A, O’Reilly AO, Reeh P, Leffler A (2010) Sodium channelopathies and pain. Pflugers Arch 460:249–263PubMedCrossRefGoogle Scholar
  72. 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 505:345–352PubMedPubMedCentralCrossRefGoogle Scholar
  73. Lipkind GM, Fozzard HA (2005) Molecular modeling of local anesthetic drug binding by voltage-gated sodium channels. Mol Pharmacol 68:1611–1622PubMedGoogle Scholar
  74. Lu Z (2004) Mechanism of rectification in inward-rectifier K+ channels. Annu Rev Physiol 66:103–129PubMedCrossRefGoogle Scholar
  75. Maier SK, Westenbroek RE, McCormick KA, Curtis R, Scheuer T, Catterall WA (2004) Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart. Circulation 109:1421–1427PubMedCrossRefGoogle Scholar
  76. Makielski JC, Limberis JT, Chang SY, Fan Z, Kyle JW (1996) Coexpression of beta 1 with cardiac sodium channel alpha subunits in oocytes decreases lidocaine block. Mol Pharmacol 49:30–39PubMedGoogle Scholar
  77. Malhotra JD, Kazen-Gillespie K, Hortsch M, Isom LL (2000) Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact. J Biol Chem 275:11383–11388PubMedCrossRefGoogle Scholar
  78. McCusker EC, Bagneris C, Naylor CE, Cole AR, D’Avanzo N, Nichols CG, Wallace BA (2012) Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing. Nat Commun 3:1102PubMedPubMedCentralCrossRefGoogle Scholar
  79. McNulty MM, Edgerton GB, Shah RD, Hanck DA, Fozzard HA, Lipkind GM (2007) Charge at the lidocaine binding site residue Phe-1759 affects permeation in human cardiac voltage-gated sodium channels. J Physiol 581:741–755PubMedPubMedCentralCrossRefGoogle Scholar
  80. McPhee JC, Ragsdale DS, Scheuer T, Catterall WA (1994) A mutation in segment IVS6 disrupts fast inactivation of sodium channels. Proc Natl Acad Sci U S A 91:12346–12350PubMedPubMedCentralCrossRefGoogle Scholar
  81. McPhee JC, Ragsdale DS, Scheuer T, Catterall WA (1995) A critical role for transmembrane segment IVS6 of the sodium channel alpha subunit in fast inactivation. J Biol Chem 270:12025–12034PubMedCrossRefGoogle Scholar
  82. 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 alpha-subunit in fast inactivation. J Biol Chem 273:1121–1129PubMedCrossRefGoogle Scholar
  83. Meisler MH, Kearney JA (2005) Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest 115:2010–2017PubMedPubMedCentralCrossRefGoogle Scholar
  84. Mitrovic N, George AL Jr, Heine R, Wagner S, Pika U, Hartlaub U, Zhou M, Lerche H, Fahlke C, Lehmann-Horn F (1994) K(+)-aggravated myotonia: destabilization of the inactivated state of the human muscle Na+ channel by the V1589M mutation. J Physiol 478:395–402PubMedPubMedCentralCrossRefGoogle Scholar
  85. 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 17:230–237PubMedPubMedCentralCrossRefGoogle Scholar
  86. Naylor CE, Bagneris C, DeCaen PG, Sula A, Scaglione A, Clapham DE, Wallace BA (2016) Molecular basis of ion permeability in a voltage-gated sodium channel. EMBO J 35:820–830PubMedPubMedCentralCrossRefGoogle Scholar
  87. Nettleton J, Wang GK (1990) PH-dependent binding of local anesthetics in single batrachotoxin-activated Na+ channels. Cocaine Vs. quaternary compounds. Biophys J 58:95–106PubMedPubMedCentralCrossRefGoogle Scholar
  88. Noda M, Shimizu S, Tanabe T, Takai T, Kayano T, Ikeda T, Takahashi H, Nakayama H, Kanaoka Y, Minamino N et al (1984) Primary structure of electrophorus electricus sodium channel deduced from CDNA sequence. Nature 312:121–127PubMedCrossRefGoogle Scholar
  89. O’Leary ME (1998) Characterization of the isoform-specific differences in the gating of neuronal and muscle sodium channels. Can J Physiol Pharmacol 76:1041–1050PubMedCrossRefGoogle Scholar
  90. O’Leary ME, Chahine M (2002) Cocaine binds to a common site on open and inactivated human heart (Na(v)1.5) sodium channels. J Physiol 541:701–716PubMedPubMedCentralCrossRefGoogle Scholar
  91. O’Leary ME, Horn R (1994) Internal block of human heart sodium channels by symmetrical tetra-alkylammoniums. J Gen Physiol 104:507–522PubMedCrossRefGoogle Scholar
  92. O’Leary ME, Kallen RG, Horn R (1994) Evidence for a direct interaction between internal tetra-alkylammonium cations and the inactivation gate of cardiac sodium channels. J Gen Physiol 104:523–539PubMedCrossRefGoogle Scholar
  93. O’Leary ME, Digregorio M, Chahine M (2003) Closing and inactivation potentiate the cocaethylene inhibition of cardiac sodium channels by distinct mechanisms. Mol Pharmacol 64:1575–1585PubMedCrossRefGoogle Scholar
  94. O’Reilly JP, Wang SY, Kallen RG, Wang GK (1999) Comparison of slow inactivation in human heart and rat skeletal muscle Na+ channel chimaeras. J Physiol 515:61–73PubMedPubMedCentralCrossRefGoogle Scholar
  95. O’Reilly JP, Wang SY, Wang GK (2001) Residue-specific effects on slow inactivation at V787 in D2-S6 of Na(v)1.4 sodium channels. Biophys J 81:2100–2111PubMedPubMedCentralCrossRefGoogle Scholar
  96. Ong BH, Tomaselli GF, Balser JR (2000) A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence. J Gen Physiol 116:653–662PubMedPubMedCentralCrossRefGoogle Scholar
  97. Patlak J (1991) Molecular kinetics of voltage-dependent Na+ channels. Physiol Rev 71:1047–1080PubMedCrossRefGoogle Scholar
  98. Patlak J, Horn R (1982) Effect of N-bromoacetamide on single sodium channel currents in excised membrane patches. J Gen Physiol 79:333–351PubMedCrossRefGoogle Scholar
  99. Pavlov E, Bladen C, Winkfein R, Diao C, Dhaliwal P, French RJ (2005) The pore, not cytoplasmic domains, underlies inactivation in a prokaryotic sodium channel. Biophys J 89:232–242PubMedPubMedCentralCrossRefGoogle Scholar
  100. Payandeh J, Scheuer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature 475:353–358PubMedPubMedCentralCrossRefGoogle Scholar
  101. Pless SA, Galpin JD, Frankel A, Ahern CA (2011) Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels. Nat Commun 2:351PubMedCrossRefGoogle Scholar
  102. Qin N, D’Andrea MR, Lubin ML, Shafaee N, Codd EE, Correa AM (2003) Molecular cloning and functional expression of the human sodium channel beta1B subunit, a novel splicing variant of the beta1 subunit. Eur J Biochem 270:4762–4770PubMedCrossRefGoogle Scholar
  103. Qu Y, Karnabi E, Chahine M, Vassalle M, Boutjdir M (2007) Expression of skeletal muscle Na(V)1.4 Na channel isoform in canine cardiac Purkinje myocytes. Biochem Biophys Res Commun 355:28–33PubMedPubMedCentralCrossRefGoogle Scholar
  104. Quan C, Mok WM, Wang GK (1996) Use-dependent inhibition of Na+ currents by benzocaine homologs. Biophys J 70:194–201PubMedPubMedCentralCrossRefGoogle Scholar
  105. Ragsdale DS, McPhee JC, Scheuer T, Catterall WA (1994) Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science 265:1724–1728PubMedCrossRefGoogle Scholar
  106. Ragsdale DS, McPhee JC, Scheuer T, Catterall WA (1996) Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels. Proc Natl Acad Sci U S A 93:9270–9275PubMedPubMedCentralCrossRefGoogle Scholar
  107. Ramos E, O’Leary ME (2004) State-dependent trapping of flecainide in the cardiac sodium channel. J Physiol 560:37–49PubMedPubMedCentralCrossRefGoogle Scholar
  108. Ren D, Navarro B, Xu H, Yue L, Shi Q, Clapham DE (2001) A prokaryotic voltage-gated sodium channel. Science 294:2372–2375PubMedCrossRefGoogle Scholar
  109. Richmond JE, Featherstone DE, Hartmann HA, Ruben PC (1998) Slow inactivation in human cardiac sodium channels. Biophys J 74:2945–2952PubMedPubMedCentralCrossRefGoogle Scholar
  110. Sandtner W, Szendroedi J, Zarrabi T, Zebedin E, Hilber K, Glaaser I, Fozzard HA, Dudley SC, Todt H (2004) Lidocaine: a foot in the door of the inner vestibule prevents ultra-slow inactivation of a voltage-gated sodium channel. Mol Pharmacol 66:648–657PubMedGoogle Scholar
  111. 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 256:1202–1205PubMedCrossRefGoogle Scholar
  112. Schoppa NE, McCormack K, Tanouye MA, Sigworth FJ (1992) The size of gating charge in wild-type and mutant Shaker potassium channels. Science 255:1712–1715PubMedCrossRefGoogle Scholar
  113. Schwarz W, Palade PT, Hille B (1977) Local anesthetics. Effect of PH on use-dependent block of sodium channels in frog muscle. Biophys J 20:343–368PubMedPubMedCentralCrossRefGoogle Scholar
  114. Shapiro BI (1977) Effects of strychnine on the sodium conductance of the frog node of ranvier. J Gen Physiol 69:915–926PubMedCrossRefGoogle Scholar
  115. Sheets MF, Kyle JW, Kallen RG, Hanck DA (1999) The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4. Biophys J 77:747–757PubMedPubMedCentralCrossRefGoogle Scholar
  116. Sheets PL, Jarecki BW, Cummins TR (2011) Lidocaine reduces the transition to slow inactivation in Na(v)1.7 voltage-gated sodium channels. Br J Pharmacol 164:719–730PubMedPubMedCentralCrossRefGoogle Scholar
  117. Shen H, Zhou Q, Pan X, Li Z, Wu J, Yan N (2017) Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution. Science 355:4326CrossRefGoogle Scholar
  118. Smith MR, Goldin AL (1997) Interaction between the sodium channel inactivation linker and domain III S4-S5. Biophys J 73:1885–1895PubMedPubMedCentralCrossRefGoogle Scholar
  119. Starmer CF, Grant AO, Strauss HC (1984) Mechanisms of use-dependent block of sodium channels in excitable membranes by local anesthetics. Biophys J 46:15–27PubMedPubMedCentralCrossRefGoogle Scholar
  120. Strichartz GR (1973) The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol 62:37–57PubMedPubMedCentralCrossRefGoogle Scholar
  121. Stuhmer W, Conti F, Suzuki H, Wang XD, Noda M, Yahagi N, Kubo H, Numa S (1989) Structural parts involved in activation and inactivation of the sodium channel. Nature 339:597–603PubMedCrossRefGoogle Scholar
  122. Sun YM, Favre I, Schild L, Moczydlowski E (1997) On the structural basis for size-selective permeation of organic cations through the voltage-gated sodium channel. Effect of alanine mutations at the DEKA locus on selectivity, inhibition by Ca2+ and H+, and molecular sieving. J Gen Physiol 110:693–715PubMedPubMedCentralCrossRefGoogle Scholar
  123. 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 108:89–104PubMedCrossRefGoogle Scholar
  124. Tanguy J, Yeh JZ (1989) QX-314 restores gating charge immobilization abolished by chloramine-T treatment in squid giant axons. Biophys J 56:421–427PubMedPubMedCentralCrossRefGoogle Scholar
  125. Tikhonov DB, Zhorov BS (2017) Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants. J Gen Physiol 149:465–481PubMedPubMedCentralCrossRefGoogle Scholar
  126. Trudeau MM, Dalton JC, Day JW, Ranum LP, Meisler MH (2006) Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation. J Med Genet 43:527–530PubMedCrossRefGoogle Scholar
  127. Ulbricht W (2005) Sodium channel inactivation: molecular determinants and modulation. Physiol Rev 85:1271–1301PubMedCrossRefGoogle Scholar
  128. Ulmschneider MB, Bagneris C, McCusker EC, DeCaen PG, Delling M, Clapham DE, Ulmschneider JP, Wallace BA (2013) Molecular dynamics of ion transport through the open conformation of a bacterial voltage-gated sodium channel. Proc Natl Acad Sci U S A 110:6364–6369PubMedPubMedCentralCrossRefGoogle Scholar
  129. Vassilev P, Scheuer T, Catterall WA (1989) Inhibition of inactivation of single sodium channels by a site-directed antibody. Proc Natl Acad Sci U S A 86:8147–8151PubMedPubMedCentralCrossRefGoogle Scholar
  130. Vedantham V, Cannon SC (1999) The position of the fast-inactivation gate during lidocaine block of voltage-gated Na+ channels. J Gen Physiol 113:7–16PubMedPubMedCentralCrossRefGoogle Scholar
  131. Vedantham V, Cannon SC (2000) Rapid and slow voltage-dependent conformational changes in segment IVS6 of voltage-gated Na(+) channels. Biophys J 78:2943–2958PubMedPubMedCentralCrossRefGoogle Scholar
  132. Veldkamp MW, Viswanathan PC, Bezzina C, Baartscheer A, Wilde AA, Balser JR (2000) Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel. Circ Res 86:E91–E97PubMedCrossRefGoogle Scholar
  133. Wang GK (1988) Cocaine-induced closures of single batrachotoxin-activated Na+ channels in planar lipid bilayers. J Gen Physiol 92:747–765PubMedCrossRefGoogle Scholar
  134. Wang SY, Mitchell J, Moczydlowski E, Wang GK (2004) Block of inactivation-deficient Na+ channels by local anesthetics in stably transfected mammalian cells: evidence for drug binding along the activation pathway. J Gen Physiol 124:691–701PubMedPubMedCentralCrossRefGoogle Scholar
  135. Watanabe E, Fujikawa A, Matsunaga H, Yasoshima Y, Sako N, Yamamoto T, Saegusa C, Noda M (2000) Nav2/NaG channel is involved in control of salt-intake behavior in the CNS. J Neurosci 20:7743–7751PubMedCrossRefGoogle Scholar
  136. 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 U S A 89:10910–10914PubMedPubMedCentralCrossRefGoogle Scholar
  137. Yang N, Horn R (1995) Evidence for voltage-dependent S4 movement in sodium channels. Neuron 15:213–218PubMedCrossRefGoogle Scholar
  138. Yang N, George AL Jr, Horn R (1996) Molecular basis of charge movement in voltage-gated sodium channels. Neuron 16:113–122PubMedCrossRefGoogle Scholar
  139. Yarov-Yarovoy V, Brown J, Sharp EM, Clare JJ, Scheuer T, Catterall WA (2001) Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na(+) channel alpha subunit. J Biol Chem 276:20–27PubMedCrossRefGoogle Scholar
  140. Yarov-Yarovoy V, McPhee JC, Idsvoog D, Pate C, Scheuer T, Catterall WA (2002) Role of amino acid residues in transmembrane segments IS6 and IIS6 of the Na+ channel alpha subunit in voltage-dependent gating and drug block. J Biol Chem 277:35393–35401PubMedCrossRefGoogle Scholar
  141. Yeh JZ, Narahashi T (1977) Kinetic analysis of pancuronium interaction with sodium channels in squid axon membranes. J Gen Physiol 69:293–323PubMedCrossRefGoogle Scholar
  142. Yeh JZ, Tanguy J (1985) Na channel activation gate modulates slow recovery from use-dependent block by local anesthetics in squid giant axons. Biophys J 47:685–694PubMedPubMedCentralCrossRefGoogle Scholar
  143. Yu FH, Catterall WA (2004) The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci STKE 2004:15Google Scholar
  144. Yu FH, Westenbroek RE, Silos-Santiago I, McCormick KA, Lawson D, Ge P, Ferriera H, Lilly J, Distefano PS, Catterall WA, Scheuer T, Curtis R (2003) Sodium channel b4, a new disulfide-linked auxiliary subunit with similarity to b2. J Neurosci 23:7577–7585PubMedCrossRefGoogle Scholar
  145. Yu FH, Yarov-Yarovoy V, Gutman GA, Catterall WA (2005) Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacol Rev 57:387–395PubMedCrossRefGoogle Scholar
  146. 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 the NaChBac voltage-gated sodium channel. Nature 486:130–134PubMedPubMedCentralCrossRefGoogle Scholar
  147. Zhou M, Morais-Cabral JH, Mann S, MacKinnon R (2001) Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. Nature 411:657–661PubMedCrossRefGoogle Scholar
  148. Zhu W, Voelker TL, Varga Z, Schubert AR, Nerbonne JM, Silva JR (2017) Mechanisms of noncovalent beta subunit regulation of NaV channel gating. J Gen Physiol 149:813.  https://doi.org/10.1085/jgp.201711802 CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Cooper Medical School of Rowan UniversityCamdenUSA
  2. 2.CERVO Brain Research CenterInstitut universitaire en santé mentale de QuébecQuebec CityCanada
  3. 3.Department of MedicineUniversité LavalQuebec CityCanada

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