A structural atlas of druggable sites on Na_v channels

References

• Catterall WA. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron. 2000 Apr;26(1):13–17. doi: 10.1016/S0896-6273(00)81133-2
   PubMed Web of Science ®Google Scholar
• Hille B. Ion channels of excitable membranes. 3rd ed. Sunderland, Mass: Sinauer; 2001.
   Google Scholar
• Hodgkin AL, Huxley AF. Resting and action potentials in single nerve fibres. J Physiol. 1945 Oct 15;104(2):176–195. doi: 10.1113/jphysiol.1945.sp004114
   PubMed Web of Science ®Google Scholar
• Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764
   PubMed Web of Science ®Google Scholar
• Hodgkin AL, Huxley AF. Currents carried by sodium and potassium ions through the membrane of the giant axon of loligo. Journal Of Physiology. 1952 Apr;116(4):449–472. doi: 10.1113/jphysiol.1952.sp004717
   PubMed Web of Science ®Google Scholar
• Hodgkin AL, Huxley AF. The components of membrane conductance in the giant axon of loligo. Journal Of Physiology. 1952 Apr;116(4):473–496. doi: 10.1113/jphysiol.1952.sp004718
   PubMed Web of Science ®Google Scholar
• Hodgkin AL, Huxley AF. The dual effect of membrane potential on sodium conductance in the giant axon of loligo. Journal Of Physiology. 1952 Apr;116(4):497–506. doi: 10.1113/jphysiol.1952.sp004719
   PubMed Web of Science ®Google Scholar
• Hille B. The permeability of the sodium channel to organic cations in myelinated nerve. J Gen Physiol. 1971 Dec;58(6):599–619. doi: 10.1085/jgp.58.6.599
   PubMed Web of Science ®Google Scholar
• Hille B. The permeability of the sodium channel to metal cations in myelinated nerve. J Gen Physiol. 1972 Jun;59(6):637–658. doi: 10.1085/jgp.59.6.637
   PubMed Web of Science ®Google Scholar
• Hille B. Ionic selectivity, saturation, and block in sodium channels. A four-barrier model. J Gen Physiol. 1975 Nov;66(5):535–560. doi: 10.1085/jgp.66.5.535
   PubMed Web of Science ®Google Scholar
• Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977 Apr;69(4):497–515. doi: 10.1085/jgp.69.4.497
   PubMed Web of Science ®Google Scholar
• Armstrong CM, Bezanilla F. Currents related to movement of the gating particles of the sodium channels. Nature. 1973 Apr 13;242(5398):459–461. doi: 10.1038/242459a0
   PubMed Web of Science ®Google Scholar
• Armstrong CM, Bezanilla F, Rojas E. Destruction of sodium conductance inactivation in squid axons perfused with pronase. J Gen Physiol. 1973 Oct;62(4):375–391. doi: 10.1085/jgp.62.4.375
   PubMed Web of Science ®Google Scholar
• Weigele JB, Barchi RL. Functional reconstitution of the purified sodium channel protein from rat sarcolemma. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3651–3655. doi: 10.1073/pnas.79.11.3651
   PubMed Web of Science ®Google Scholar
• Tamkun MM, Catterall WA. Reconstitution of the voltage-sensitive sodium channel of rat brain from solubilized components. J Biol Chem. 1981 Nov 25;256(22):11457–11463. doi: 10.1016/S0021-9258(19)68422-X
   PubMed Web of Science ®Google Scholar
• Noda M, Shimizu S, Tanabe T, et al. Primary structure of electrophorus electricus sodium channel deduced from cDNA sequence. Nature. 1984 Nov 8-14;312(5990):121–127. doi: 10.1038/312121a0
   PubMed Web of Science ®Google Scholar
• Yu FH, Yarov-Yarovoy V, Gutman GA, et al. Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacol Rev. 2005 Dec;57(4):387–395. doi: 10.1124/pr.57.4.13
   PubMed Web of Science ®Google Scholar
• Yu FH, Catterall WA. The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci STKE. 2004 Oct 5;2004(253):re15. doi: 10.1126/stke.2532004re15
   PubMedGoogle Scholar
• Hartshorne RP, Catterall WA. The sodium channel from rat brain. Purification and subunit composition. J Biol Chem. 1984 Feb 10;259(3):1667–1675. doi: 10.1016/S0021-9258(17)43460-0
   PubMed Web of Science ®Google Scholar
• Isom LL, De Jongh KS, Catterall WA. Auxiliary subunits of voltage-gated ion channels. Neuron. 1994 Jun;12(6):1183–1194. doi: 10.1016/0896-6273(94)90436-7
   PubMed Web of Science ®Google Scholar
• O’Malley HA, Isom LL. Sodium channel β subunits: emerging targets in channelopathies. Annu Rev Physiol. 2015;77(1):481–504. doi: 10.1146/annurev-physiol-021014-071846
   PubMedGoogle Scholar
• Pettersen EF, Goddard TD, Huang CC, et al. UCSF chimera–a visualization system for exploratory research and analysis. J Comput Chem. 2004 Oct;25(13):1605–1612. doi: 10.1002/jcc.20084
   PubMed Web of Science ®Google Scholar
• Noda M, Ikeda T, Kayano T, et al. Existence of distinct sodium channel messenger RNAs in rat brain. Nature. 1986 Mar 13-19;320(6058):188–192. doi: 10.1038/320188a0
   PubMed Web of Science ®Google Scholar
• Payandeh J, Scheuer T, Zheng N, et al. The crystal structure of a voltage-gated sodium channel. Nature. 2011 Jul 10;475(7356):353–358. doi: 10.1038/nature10238
   PubMed Web of Science ®Google Scholar
• Zhang X, Ren W, DeCaen P, et al. Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature. 2012 May 20;486(7401):130–134. doi: 10.1038/nature11054
   PubMed Web of Science ®Google Scholar
• Favre I, Moczydlowski E, Schild L. On the structural basis for ionic selectivity among Na+, K+, and Ca2+ in the voltage-gated sodium channel. Biophys J. 1996 Dec;71(6):3110–3125. doi: 10.1016/S0006-3495(96)79505-X
   PubMed Web of Science ®Google Scholar
• Sun YM, Favre I, Schild L, et al. 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. 1997 Dec;110(6):693–715. doi: 10.1085/jgp.110.6.693
   PubMed Web of Science ®Google Scholar
• Heinemann SH, Terlau H, Stuhmer W, et al. Calcium channel characteristics conferred on the sodium channel by single mutations. Nature. 1992 Apr 2;356(6368):441–443. doi: 10.1038/356441a0
   PubMed Web of Science ®Google Scholar
• West JW, Patton DE, Scheuer T, et al. A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10910–10914. doi: 10.1073/pnas.89.22.10910
   PubMed Web of Science ®Google Scholar
• Goldin AL. Mechanisms of sodium channel inactivation. Curr Opin Neurobiol. 2003 Jun;13(3):284–290. doi: 10.1016/S0959-4388(03)00065-5
   PubMed Web of Science ®Google Scholar
• West JW, Patton DE, Scheuer T, et al. A cluster of hydrophobic amino-acid-residues required for fast Na±Channel inactivation. P Natl Acad Sci USA. 1992 Nov 15;89(22):10910–10914. doi: 10.1073/pnas.89.22.10910
   PubMed Web of Science ®Google Scholar
• Hartmann HA, Tiedeman AA, Chen SF, et al. Effects of iii-iv linker mutations on human heart Na+ channel inactivation gating. Circ Res. 1994 Jul;75(1):114–122. doi: 10.1161/01.RES.75.1.114
   PubMed Web of Science ®Google Scholar
• Catterall WA, Goldin AL, Waxman SG. International union of pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev. 2005 Dec;57(4):397–409. doi: 10.1124/pr.57.4.4
   PubMed Web of Science ®Google Scholar
• Denac H, Mevissen M, Scholtysik G. Structure, function and pharmacology of voltage-gated sodium channels. Naunyn Schmiedebergs Arch Pharmacol. 2000 Dec;362(6):453–479. doi: 10.1007/s002100000319
   PubMed Web of Science ®Google Scholar
• Catterall WA. Voltage-gated sodium channels at 60: structure, function and pathophysiology. Journal Of Physiology. 2012 Jun 1;590(11):2577–2589. doi: 10.1113/jphysiol.2011.224204
   PubMed Web of Science ®Google Scholar
• Huang W, Liu M, Yan SF, et al. Structure-based assessment of disease-related mutations in human voltage-gated sodium channels. Protein & Cell. 2017 Jun;8(6):401–438. doi: 10.1007/s13238-017-0372-z
   PubMed Web of Science ®Google Scholar
• Catterall WA, Kalume F, Oakley JC. NaV1.1 channels and epilepsy. Journal Of Physiology. 2010 Jun 1;588(Pt 11):1849–1859. doi: 10.1113/jphysiol.2010.187484
   PubMed Web of Science ®Google Scholar
• Menezes LFS, Sabia Junior EF, Tibery DV, et al. Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review. Front Pharmacol. 2020;11:1276. doi: 10.3389/fphar.2020.01276
   PubMed Web of Science ®Google Scholar
• Tfelt-Hansen J, Winkel BG, Grunnet M, et al. Inherited cardiac diseases caused by mutations in the Nav1.5 sodium channel. J Cardiovasc Electrophysiol. 2010 Jan;21(1):107–115. doi: 10.1111/j.1540-8167.2009.01633.x
   PubMed Web of Science ®Google Scholar
• Savio-Galimberti E, Argenziano M, Antzelevitch C. Cardiac arrhythmias related to sodium channel dysfunction. Handb Exp Pharmacol. 2018;246:331–354.
   PubMedGoogle Scholar
• Cox JJ, Reimann F, Nicholas AK, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006 Dec 14;444(7121):894–898. doi: 10.1038/nature05413
   PubMed Web of Science ®Google Scholar
• Basbaum AI, Bautista DM, Scherrer G, et al. Cellular and molecular mechanisms of pain. Cell. 2009 Oct 16;139(2):267–284. doi: 10.1016/j.cell.2009.09.028
   PubMed Web of Science ®Google Scholar
• Dib-Hajj SD, Waxman SG. Sodium channels in human pain disorders: genetics and pharmacogenomics. Annu Rev Neurosci. 2019 Jul 8;42(1):87–106. doi: 10.1146/annurev-neuro-070918-050144
   PubMedGoogle Scholar
• Bagal SK, Marron BE, Owen RM, et al. Voltage gated sodium channels as drug discovery targets. Channels. 2015 Nov 2;9(6):360–366. doi: 10.1080/19336950.2015.1079674
   PubMed Web of Science ®Google Scholar
• Clare JJ, Tate SN, Nobbs M, et al. Voltage-gated sodium channels as therapeutic targets. Drug Discovery Today. 2000 Nov;5(11):506–520. doi: 10.1016/S1359-6446(00)01570-1
   PubMed Web of Science ®Google Scholar
• de Lera Ruiz M, Kraus RL. Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications. J Med Chem. 2015 Sep 24;58(18):7093–7118. doi: 10.1021/jm501981g
   PubMed Web of Science ®Google Scholar
• Savio-Galimberti E, Gollob MH, Darbar D. Voltage-gated sodium channels: biophysics, pharmacology, and related channelopathies. Front Pharmacol. 2012;3:124. doi: 10.3389/fphar.2012.00124
   PubMed Web of Science ®Google Scholar
• Bagal SK, Marron BE, Owen RM, et al. Voltage gated sodium channels as drug discovery targets. Channels (Austin). 2015;9(6):360–366. doi: 10.1080/19336950.2015.1079674
   PubMed Web of Science ®Google Scholar
• Liao M, Cao E, Julius D, et al. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature. 2013 Dec 5;504(7478):107–112. doi: 10.1038/nature12822
   PubMed Web of Science ®Google Scholar
• Kuhlbrandt W. Cryo-EM enters a new era. Elife. 2014 Aug 13;3:e03678. doi: 10.7554/eLife.03678
   PubMed Web of Science ®Google Scholar
• Scheres SH. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J Struct Biol. 2012 Dec;180(3):519–530. doi: 10.1016/j.jsb.2012.09.006
   PubMed Web of Science ®Google Scholar
• Shen H, Zhou Q, Pan X, et al. Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution. Science. 2017 Mar 3;355(6328). doi: 10.1126/science.aal4326
   Web of Science ®Google Scholar
• Yan Z, Zhou Q, Wang L, et al. Structure of the Nav1.4-beta1 complex from electric Eel. Cell. 2017 Jul 27;170(3):470–482 e11. doi: 10.1016/j.cell.2017.06.039
   PubMed Web of Science ®Google Scholar
• Li Z, Jin X, Wu T, et al. Structure of human Na(v)1.5 reveals the fast inactivation-related segments as a mutational hotspot for the long QT syndrome. Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). doi: 10.1073/pnas.2100069118
   Web of Science ®Google Scholar
• Pan X, Li Z, Zhou Q, et al. Structure of the human voltage-gated sodium channel Nav1.4 in complex with beta1 [Research support, non-U.S. Gov’t]. Science. 2018 Oct 19;362(6412). doi: 10.1126/science.aau2486
   Web of Science ®Google Scholar
• Shen H, Liu D, Wu K, et al. Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins. Science. 2019 Mar 22;363(6433):1303–1308. doi: 10.1126/science.aaw2493
   PubMed Web of Science ®Google Scholar
• Pan X, Li Z, Huang X, et al. Molecular basis for pore blockade of human Na(+) channel Nav1.2 by the mu-conotoxin KIIIA. Science. 2019 Mar 22;363(6433):1309–1313. doi: 10.1126/science.aaw2999
   PubMed Web of Science ®Google Scholar
• Pan X, Li Z, Jin X, et al. Comparative structural analysis of human Nav1.1 and Nav1.5 reveals mutational hotspots for sodium channelopathies. Proc Natl Acad Sci. 2021 Mar 16;118(11): e2100066118. doi: 10.1073/pnas.2100066118
   Web of Science ®Google Scholar
• Huang X, Jin X, Huang G, et al. Structural basis for high-voltage activation and subtype-specific inhibition of human Nav1.8. Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2208211119. doi: 10.1073/pnas.2208211119
   PubMed Web of Science ®Google Scholar
• Fan X, Huang J, Jin X, et al. Cryo-EM structure of human voltage-gated sodium channel Na(v)1.6. Proc Natl Acad Sci U S A. 2023 Jan 31;120(5):e2220578120. doi: 10.1073/pnas.2220578120
   PubMed Web of Science ®Google Scholar
• Jiang D, Shi H, Tonggu L, et al. Structure of the cardiac sodium channel. Cell. 2020 Jan 9;180(1):122–134 e10. doi: 10.1016/j.cell.2019.11.041
   PubMed Web of Science ®Google Scholar
• Li X, Xu F, Xu H, et al. Structural basis for modulation of human Na(V)1.3 by clinical drug and selective antagonist. Nat Commun. 2022 Mar 11;13(1):1286. doi: 10.1038/s41467-022-28808-5
   PubMed Web of Science ®Google Scholar
• Shen H, Li Z, Jiang Y, et al. Structural basis for the modulation of voltage-gated sodium channels by animal toxins [Research support, non-U.S. Gov’t]. Science. 2018 Oct 19;362(6412). doi: 10.1126/science.aau2596
   Web of Science ®Google Scholar
• Huang G, Liu D, Wang W, et al. High-resolution structures of human Na(v)1.7 reveal gating modulation through alpha-pi helical transition of S6(IV). Cell Rep. 2022 Apr 26;39(4):110735. doi: 10.1016/j.celrep.2022.110735
   PubMedGoogle Scholar
• Li Y, Yuan T, Huang B, et al. Structure of human Na(V)1.6 channel reveals Na(+) selectivity and pore blockade by 4,9-anhydro-tetrodotoxin. Nat Commun. 2023 Feb 23;14(1):1030. doi: 10.1038/s41467-023-36766-9
   PubMed Web of Science ®Google Scholar
• Li Z, Jin X, Wu T, et al. Structural basis for pore blockade of the human cardiac sodium channel Nav 1.5 by the antiarrhythmic drug quinidine*. Angew Chem Int Ed Engl. 2021 May 10;60(20):11474–11480. doi: 10.1002/anie.202102196
   PubMed Web of Science ®Google Scholar
• Wu Q, Huang J, Fan X, et al. Structural mapping of Na(v)1.7 antagonists. Nat Commun. 2023 Jun 3;14(1):3224. doi: 10.1038/s41467-023-38942-3
   PubMed Web of Science ®Google Scholar
• Zhang J, Shi Y, Huang Z, et al. Structural basis for Na(V)1.7 inhibition by pore blockers. Nat Struct Mol Biol. 2022 Dec;29(12):1208–1216. doi: 10.1038/s41594-022-00860-1
   PubMed Web of Science ®Google Scholar
• Huang J, Fan X, Jin X, et al. Dual-pocket inhibition of Na(v) channels by the antiepileptic drug lamotrigine. Proc Natl Acad Sci U S A. 2023 Oct 10;120(41):e2309773120. doi: 10.1073/pnas.2309773120
   PubMedGoogle Scholar
• Jiang D, Banh R, Gamal El-Din TM, et al. Open-state structure and pore gating mechanism of the cardiac sodium channel. Cell. 2021 Sep 30;184(20):5151–5162 e11. doi: 10.1016/j.cell.2021.08.021
   PubMed Web of Science ®Google Scholar
• Huang J, Fan X, Jin X, et al. Cannabidiol inhibits Na(v) channels through two distinct binding sites. Nat Commun. 2023 Jun 17;14(1):3613. doi: 10.1038/s41467-023-39307-6
   PubMed Web of Science ®Google Scholar
• Gao S, Valinsky WC, On NC, et al. Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated Na(+) channels in nanodisc. Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14187–14193. doi: 10.1073/pnas.1922903117
   PubMed Web of Science ®Google Scholar
• Xu H, Li T, Rohou A, et al. Structural basis of Nav1.7 inhibition by a gating-modifier spider toxin. Cell. 2019 Feb 7;176(4):702–715 e14. doi: 10.1016/j.cell.2018.12.018
   PubMed Web of Science ®Google Scholar
• Wisedchaisri G, Tonggu L, Gamal El-Din TM, et al. Structural basis for high-affinity trapping of the Na(V)1.7 channel in its resting state by Tarantula Toxin. Mol Cell. 2021 Jan 7;81(1):38–48 e4. doi: 10.1016/j.molcel.2020.10.039
   PubMed Web of Science ®Google Scholar
• Clairfeuille T, Cloake A, Infield DT, et al. Structural basis of alpha-scorpion toxin action on Na(v) channels. Science. 2019 Mar 22;363(6433). doi: 10.1126/science.aav8573
   PubMed Web of Science ®Google Scholar
• Jiang D, Tonggu L, Gamal El-Din TM, et al. Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin. Nat Commun. 2021 Jan 4;12(1):128. doi: 10.1038/s41467-020-20078-3
   PubMed Web of Science ®Google Scholar
• Ahuja S, Mukund S, Deng L, et al. Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist. Science. 2015 Dec 18;350(6267):aac5464. doi: 10.1126/science.aac5464
   PubMed Web of Science ®Google Scholar
• Kschonsak M, Jao CC, Arthur CP, et al. Cryo-EM reveals an unprecedented binding site for Na(V)1.7 inhibitors enabling rational design of potent hybrid inhibitors. Elife. 2023 Mar 12;28:e84151. doi: 10.7554/eLife.84151
   Web of Science ®Google Scholar
• Cestele S, Catterall WA. Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie. 2000 Sep-Oct;82(9–10):883–892. doi: 10.1016/S0300-9084(00)01174-3
   PubMed Web of Science ®Google Scholar
• Clare JJ, Tate SN, Nobbs M, et al. Voltage-gated sodium channels as therapeutic targets. Drug Discov Today. 2000 Nov 1;5(11):506–520. doi: 10.1016/S1359-6446(00)01570-1
   PubMed Web of Science ®Google Scholar
• Santos R, Ursu O, Gaulton A, et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov. 2017 Jan;16(1):19–34. doi: 10.1038/nrd.2016.230
   PubMed Web of Science ®Google Scholar
• McKerrall SJ, Sutherlin DP. Na(v)1.7 inhibitors for the treatment of chronic pain. Bioorg Med Chem Lett. 2018 Oct 15;28(19):3141–3149. doi: 10.1016/j.bmcl.2018.08.007
   PubMed Web of Science ®Google Scholar
• Zhang F, Xu X, Li T, et al. Shellfish toxins targeting voltage-gated sodium channels. Mar Drugs. 2013 Nov 28;11(12):4698–4723. doi: 10.3390/md11124698
   PubMed Web of Science ®Google Scholar
• Noreng S, Li TB, Payandeh J. Structural Pharmacology of Voltage-Gated Sodium Channels. J Mol Biol. 2021 Aug 20;433(17):166967. doi: 10.1016/j.jmb.2021.166967
   PubMed Web of Science ®Google Scholar
• Ruiz MD, Kraus RL. Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications. J Med Chem. 2015 Sep 24;58(18):7093–7118. doi: 10.1021/jm501981g
   PubMed Web of Science ®Google Scholar
• Xu H, Li T, Rohou A, et al. Structural basis of Nav1.7 inhibition by a gating-modifier spider toxin. Cell. 2019 Feb 21;176(5):1238–1239. doi: 10.1016/j.cell.2019.01.047
   PubMed Web of Science ®Google Scholar
• Zhang MM, Green BR, Catlin P, et al. Structure/Function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. J Biol Chem. 2007 Oct 19;282(42):30699–30706. doi: 10.1074/jbc.M704616200
   PubMed Web of Science ®Google Scholar
• McArthur JR, Singh G, McMaster D, et al. Interactions of key charged residues contributing to selective block of neuronal sodium channels by mu-conotoxin KIIIA. Mol Pharmacol. 2011 Oct;80(4):573–584. doi: 10.1124/mol.111.073460
   PubMed Web of Science ®Google Scholar
• Khoo KK, Gupta K, Green BR, et al. Distinct disulfide isomers of mu-conotoxins KIIIA and KIIIB block voltage-gated sodium channels. Biochemistry. 2012 Dec 11;51(49):9826–9835. doi: 10.1021/bi301256s
   PubMed Web of Science ®Google Scholar
• Zhang J, Mao W, Ren Y, et al. Simulating the ion permeation and ion selection for a eukaryotic voltage-gated sodium channel Na(V)PaS. Protein & Cell. 2018 Jun;9(6):580–585. doi: 10.1007/s13238-018-0522-y
   PubMed Web of Science ®Google Scholar
• Banerjee A, Lee A, Campbell E, et al. Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K(+) channel. Elife. 2013 May 21;2:e00594. doi: 10.7554/eLife.00594
   PubMed Web of Science ®Google Scholar
• Hille B. The receptor for tetrodotoxin and saxitoxin. A structural hypothesis. Biophys J. 1975 Jun;15(6):615–619. doi: 10.1016/S0006-3495(75)85842-5
   PubMed Web of Science ®Google Scholar
• Reed JK, Raftery MA. Properties of the tetrodotoxin binding component in plasma membranes isolated from electrophorus electricus. Biochemistry. 1976 Mar 9;15(5):944–953. doi: 10.1021/bi00650a002
   PubMed Web of Science ®Google Scholar
• Duran-Riveroll LM, Cembella AD. Guanidinium toxins and their interactions with Voltage-Gated Sodium Ion Channels. Mar Drugs. 2017 Oct 13;15(10):303. doi: 10.3390/md15100303
   PubMed Web of Science ®Google Scholar
• Satin J, Kyle JW, Chen M, et al. A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties. Science. 1992 May 22;256(5060):1202–1205. doi: 10.1126/science.256.5060.1202
   PubMed Web of Science ®Google Scholar
• Blair NT, Bean BP. Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potentials of nociceptive sensory neurons. J Neurosci. 2002 Dec 1;22(23):10277–10290. doi: 10.1523/JNEUROSCI.22-23-10277.2002
   PubMed Web of Science ®Google Scholar
• Walker JR, Novick PA, Parsons WH, et al. Marked difference in saxitoxin and tetrodotoxin affinity for the human nociceptive voltage-gated sodium channel (Nav1.7) [corrected]. Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18102–18107. doi: 10.1073/pnas.1206952109
   PubMed Web of Science ®Google Scholar
• Beckley JT, Pajouhesh H, Luu G, et al. Antinociceptive properties of an isoform-selective inhibitor of Nav1.7 derived from saxitoxin in mouse models of pain. Pain. 2021 Apr 1;162(4):1250–1261. doi: 10.1097/j.pain.0000000000002112
   PubMed Web of Science ®Google Scholar
• Hondeghem L, Katzung BG. Test of a model of antiarrhythmic drug action. Effects of quinidine and lidocaine on myocardial conduction. Circulation. 1980 Jun;61(6):1217–1224. doi: 10.1161/01.CIR.61.6.1217
   PubMed Web of Science ®Google Scholar
• Clarkson CW, Hondeghem LM. Evidence for a specific receptor site for lidocaine, quinidine, and bupivacaine associated with cardiac sodium channels in guinea pig ventricular myocardium. Circ Res. 1985 Apr;56(4):496–506. doi: 10.1161/01.RES.56.4.496
   PubMed Web of Science ®Google Scholar
• Grace AA, Camm AJ. Quinidine. N Engl J Med. 1998 Jan 1;338(1):35–45. doi: 10.1056/NEJM199801013380107
   PubMed Web of Science ®Google Scholar
• Anno T, Hondeghem LM. Interactions of flecainide with guinea pig cardiac sodium channels. Importance of activation unblocking to the voltage dependence of recovery. Circ Res. 1990 Mar;66(3):789–803. doi: 10.1161/01.RES.66.3.789
   PubMed Web of Science ®Google Scholar
• Konzen G, Reichardt B, Hauswirth O. Fast and slow blockade of sodium channels by flecainide in rabbit cardiac Purkinje fibres. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jun;341(6):565–576. doi: 10.1007/BF00171738
   PubMed Web of Science ®Google Scholar
• Kohlhardt M, Fichtner H. Block of single cardiac Na+ channels by antiarrhythmic drugs: the effect of amiodarone, propafenone and diprafenone. J Membr Biol. 1988 May;102(2):105–119. doi: 10.1007/BF01870449
   PubMed Web of Science ®Google Scholar
• Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012 Mar 14;2012(3). CD001447. doi: 10.1002/14651858.CD001447.pub3.
   PubMedGoogle Scholar
• Carboni M, Zhang ZS, Neplioueva V, et al. Slow sodium channel inactivation and use-dependent block modulated by the same domain IVS6 residue. J Membrane Biol. 2005 Sep;207(2):107–117. doi: 10.1007/s00232-005-0805-0
   PubMed Web of Science ®Google Scholar
• Chahine M, Poulin H. Prozac blocks Nav1.5 channels via a mechanism similar to that of class 1 antiarrhythmics. Fund Clin Pharmacol. 2014 May;28(2):31–31. doi: 10.1016/j.bpj.2013.11.1874
   Google Scholar
• Schulze V, Stoetzer C, O’Reilly AO, et al. The opioid methadone induces a local anaesthetic-like inhibition of the cardiac Nav channel, Nav1.5. Brit J Pharmacol. 2014 Jan;171(2):427–437. doi: 10.1111/bph.12465
   PubMed Web of Science ®Google Scholar
• Devinsky O, Cross JH, Wright S. Trial of Cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017 Aug 17;377(7):699–700
   PubMed Web of Science ®Google Scholar
• Devinsky O, Cross JH, Laux L, et al. Trial of Cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017 May 25;376(21):2011–2020. doi: 10.1056/NEJMoa1611618
   PubMed Web of Science ®Google Scholar
• Devinsky O, Patel AD, Cross JH, et al. Effect of Cannabidiol on drop seizures in the lennox-gastaut syndrome. N Engl J Med. 2018 May 17;378(20):1888–1897. doi: 10.1056/NEJMoa1714631
   PubMed Web of Science ®Google Scholar
• Ghovanloo MR, Shuart NG, Mezeyova J, et al. Inhibitory effects of cannabidiol on voltage-dependent sodium currents. J Biol Chem. 2018 Oct 26;293(43):16546–16558. doi: 10.1074/jbc.RA118.004929
   PubMed Web of Science ®Google Scholar
• Mason ER, Cummins TR. Differential inhibition of human Nav1.2 resurgent and persistent sodium currents by Cannabidiol and GS967. Int J Mol Sci. 2020 Apr 1;21(7):2454. doi: 10.3390/ijms21072454
   PubMed Web of Science ®Google Scholar
• El-Din TMG, Lenaeus MJ, Zheng N, et al. Fenestrations control resting-state block of a voltage-gated sodium channel. P Natl Acad Sci USA. 2018 Dec 18;115(51):13111–13116. doi: 10.1073/pnas.1814928115
   PubMed Web of Science ®Google Scholar
• El-Din TMG, Lenaeus MJ, Zheng N, et al. Fenestrations control the resting state block of a voltage gated sodium channel. Biophys J. 2019 Feb 15;116(3):172a–172a. doi: 10.1016/j.bpj.2018.11.957
   Web of Science ®Google Scholar
• Al-Kuraishy HM, Al-Gareeb AI, Naji MT, et al. Role of vinpocetine in ischemic stroke and poststroke outcomes: a critical review. Brain Circ. 2020 Jan-Mar;6(1):1–10. doi: 10.4103/bc.bc_46_19
   PubMedGoogle Scholar
• Cai S, Bellampalli SS, Yu J, et al. (-)-Hardwickiic Acid and Hautriwaic Acid Induce Antinociception via Blockade of Tetrodotoxin-Sensitive Voltage-Dependent Sodium Channels. ACS Chem Neurosci. 2019 Mar 20;10(3):1716–1728. doi: 10.1021/acschemneuro.8b00617
   PubMed Web of Science ®Google Scholar
• Chowdhury S, Chafeev M, Liu S, et al. Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3676–3681. doi: 10.1016/j.bmcl.2011.04.088
   PubMed Web of Science ®Google Scholar
• Bregman H, Berry L, Buchanan JL, et al. Identification of a potent, state-dependent inhibitor of Nav1.7 with oral efficacy in the formalin model of persistent pain. J Med Chem. 2011 Jul 14;54(13):4427–4445. doi: 10.1021/jm200018k
   PubMed Web of Science ®Google Scholar
• Hinckley CA, Kuryshev Y, Sers A, et al. Characterization of vixotrigine, a Broad-Spectrum voltage-gated sodium channel blocker. Mol Pharmacol. 2021 Jan;99(1):49–59. doi: 10.1124/molpharm.120.000079
   PubMed Web of Science ®Google Scholar
• Tang XC, Liu XJ, Lu WH, et al. Studies on the analgesic action and physical dependence of bulleyaconitine a. Yao Xue Xue Bao. 1986 Dec;21(12):886–891.
   PubMedGoogle Scholar
• Wang CF, Gerner P, Wang SY, et al. Bulleyaconitine a isolated from aconitum plant displays long-acting local anesthetic properties in vitro and in vivo. Anesthesiology. 2007 Jul;107(1):82–90. doi: 10.1097/01.anes.0000267502.18605.ad
   PubMed Web of Science ®Google Scholar
• Yang N, George AL Jr., Horn R. Molecular basis of charge movement in voltage-gated sodium channels. Neuron. 1996 Jan;16(1):113–122. doi: 10.1016/S0896-6273(00)80028-8
   PubMed Web of Science ®Google Scholar
• Catterall WA, Wisedchaisri G, Zheng N. The chemical basis for electrical signaling. Nat Chem Biol. 2017 Apr 13;13(5):455–463. doi: 10.1038/nchembio.2353
   PubMed Web of Science ®Google Scholar
• Arhem P. Voltage sensing in ion channels: a 50-year-old mystery resolved? Lancet. 2004 Apr 10;363(9416):1221–1223. doi: 10.1016/S0140-6736(04)15954-0
   PubMed Web of Science ®Google Scholar
• Ahern CA, Payandeh J, Bosmans F, et al. The hitchhiker’s guide to the voltage-gated sodium channel galaxy. J Gen Physiol. 2016 Jan;147(1):1–24. doi: 10.1085/jgp.201511492
   PubMed Web of Science ®Google Scholar
• Cestele S, Qu Y, Rogers JC, et al. Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II. Neuron. 1998 Oct;21(4):919–931. doi: 10.1016/S0896-6273(00)80606-6
   PubMed Web of Science ®Google Scholar
• Bosmans F, Martin-Eauclaire MF, Swartz KJ. Deconstructing voltage sensor function and pharmacology in sodium channels. Nature. 2008 Nov 13;456(7219):202–208. doi: 10.1038/nature07473
   PubMed Web of Science ®Google Scholar
• Wang J, Yarov-Yarovoy V, Kahn R, et al. Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage sensor. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15426–15431. doi: 10.1073/pnas.1112320108
   PubMed Web of Science ®Google Scholar
• Catterall WA, Cestele S, Yarov-Yarovoy V, et al. Voltage-gated ion channels and gating modifier toxins. Toxicon. 2007 Feb;49(2):124–141. doi: 10.1016/j.toxicon.2006.09.022
   PubMed Web of Science ®Google Scholar
• Bende NS, Dziemborowicz S, Mobli M, et al. A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a. Nat Commun. 2014 Jul 11;5(1):4350. doi: 10.1038/ncomms5350
   PubMedGoogle Scholar
• Peng K, Shu Q, Liu Z, et al. Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena. J Biol Chem. 2002 Dec 6;277(49):47564–47571. doi: 10.1074/jbc.M204063200
   PubMed Web of Science ®Google Scholar
• Chen H, Heinemann SH. Interaction of scorpion alpha-toxins with cardiac sodium channels: binding properties and enhancement of slow inactivation. J Gen Physiol. 2001 Jun;117(6):505–518. doi: 10.1085/jgp.117.6.505
   PubMed Web of Science ®Google Scholar
• Mannikko R, Shenkarev ZO, Thor MG, et al. Spider toxin inhibits gating pore currents underlying periodic paralysis. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4495–4500. doi: 10.1073/pnas.1720185115
   PubMed Web of Science ®Google Scholar
• McCormack K, Santos S, Chapman ML, et al. Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):E2724–32. doi: 10.1073/pnas.1220844110
   PubMed Web of Science ®Google Scholar
• Alsaloum M, Higerd GP, Effraim PR, et al. Status of peripheral sodium channel blockers for non-addictive pain treatment. Nat Rev Neurol. 2020 Dec;16(12):689–705. doi: 10.1038/s41582-020-00415-2
   PubMed Web of Science ®Google Scholar
• Huang G, Wu Q, Li Z, et al. Unwinding and spiral sliding of S4 and domain rotation of VSD during the electromechanical coupling in Na(v)1.7. Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2209164119. doi: 10.1073/pnas.2209164119
   PubMed Web of Science ®Google Scholar