{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T15:12:41Z","timestamp":1793200361653,"version":"4.5.0"},"reference-count":167,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Voltage-gated sodium (Na\n                    <jats:sub>V<\/jats:sub>\n                    ) channels are responsible for the rapid rising-phase of action potentials in excitable cells. Over 1,000 mutations in Na\n                    <jats:sub>V<\/jats:sub>\n                    channels are associated with human diseases including epilepsy, periodic paralysis, arrhythmias and pain disorders. Natural toxins and clinically-used small-molecule drugs bind to Na\n                    <jats:sub>V<\/jats:sub>\n                    channels and modulate their functions. Recent advances from cryo-electron microscopy (cryo-EM) structures of Na\n                    <jats:sub>V<\/jats:sub>\n                    channels reveal invaluable insights into the architecture, activation, fast inactivation, electromechanical coupling, ligand modulation and pharmacology of eukaryotic Na\n                    <jats:sub>V<\/jats:sub>\n                    channels. These structural analyses not only demonstrate molecular mechanisms for Na\n                    <jats:sub>V<\/jats:sub>\n                    channel structure and function, but also provide atomic level templates for rational development of potential subtype-selective therapeutics. In this review, we summarize recent structural advances of eukaryotic Na\n                    <jats:sub>V<\/jats:sub>\n                    channels, highlighting the structural features of eukaryotic Na\n                    <jats:sub>V<\/jats:sub>\n                    channels as well as distinct modulation mechanisms by a wide range of modulators from natural toxins to synthetic small-molecules.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.908867","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T03:52:17Z","timestamp":1654228337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Structural Advances in Voltage-Gated Sodium Channels"],"prefix":"10.3389","volume":"13","author":[{"given":"Daohua","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanyi","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1085\/jgp.201511492","article-title":"The Hitchhiker's Guide to the Voltage-Gated Sodium Channel Galaxy","volume":"147","author":"Ahern","year":"2016","journal-title":"J. Gen. Physiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"aac5464","DOI":"10.1126\/science.aac5464","article-title":"Structural Basis of Nav1.7 Inhibition by an Isoform-Selective Small-Molecule Antagonist","volume":"350","author":"Ahuja","year":"2015","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0152405","DOI":"10.1371\/journal.pone.0152405","article-title":"Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release","volume":"11","author":"Alexandrou","year":"2016","journal-title":"PLoS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/s41582-020-00415-2","article-title":"Status of Peripheral Sodium Channel Blockers for Non-addictive Pain Treatment","volume":"16","author":"Alsaloum","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/242459a0","article-title":"Currents Related to Movement of the Gating Particles of the Sodium Channels","volume":"242","author":"Armstrong","year":"1973","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1085\/jgp.62.4.375","article-title":"Destruction of Sodium Conductance Inactivation in Squid Axons Perfused with Pronase","volume":"62","author":"Armstrong","year":"1973","journal-title":"J. Gen. Physiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"8428","DOI":"10.1073\/pnas.1406855111","article-title":"Prokaryotic NavMs Channel as a Structural and Functional Model for Eukaryotic Sodium Channel Antagonism","volume":"111","author":"Bagn\u00e9ris","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1152\/physrev.00052.2017","article-title":"The Role of Voltage-Gated Sodium Channels in Pain Signaling","volume":"99","author":"Bennett","year":"2019","journal-title":"Physiol. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1074\/jbc.273.1.80","article-title":"A Specific Interaction between the Cardiac Sodium Channel and Site-3 Toxin Anthopleurin B","volume":"273","author":"Benzinger","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"13057","DOI":"10.1073\/pnas.1408710111","article-title":"Local Anesthetic and Antiepileptic Drug Access and Binding to a Bacterial Voltage-Gated Sodium Channel","volume":"111","author":"Boiteux","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B11","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1085\/jgp.201310998","article-title":"Domain IV Voltage-Sensor Movement Is Both Sufficient and Rate Limiting for Fast Inactivation in Sodium Channels","volume":"142","author":"Capes","year":"2013","journal-title":"J. Gen. Physiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.toxicon.2006.09.022","article-title":"Voltage-gated Ion Channels and Gating Modifier Toxins","volume":"49","author":"Catterall","year":"2007","journal-title":"Toxicon"},{"key":"B13","doi-asserted-by":"publisher","first-page":"11768","DOI":"10.1523\/JNEUROSCI.3901-08.2008","article-title":"Inherited Neuronal Ion Channelopathies: New Windows on Complex Neurological Diseases","volume":"28","author":"Catterall","year":"2008","journal-title":"J. Neurosci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/s0896-6273(00)81133-2","article-title":"From Ionic Currents to Molecular Mechanisms: the Structure and Function of Voltage-Gated Sodium Channels","volume":"26","author":"Catterall","year":"2000","journal-title":"Neuron"},{"key":"B15","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1124\/pr.57.4.4","article-title":"International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels","volume":"57","author":"Catterall","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1146\/annurev-pharmtox-010818-021757","article-title":"Structure and Pharmacology of Voltage-Gated Sodium and Calcium Channels","volume":"60","author":"Catterall","year":"","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1146\/annurev.bi.55.070186.004513","article-title":"Molecular Properties of Voltage-Sensitive Sodium Channels","volume":"55","author":"Catterall","year":"1986","journal-title":"Annu. Rev. Biochem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1146\/annurev-pharmtox-011112-140232","article-title":"Sodium Channels, Inherited Epilepsy, and Antiepileptic Drugs","volume":"54","author":"Catterall","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nchembio.2353","article-title":"The Chemical Basis for Electrical Signaling","volume":"13","author":"Catterall","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1038\/s41589-020-0644-4","article-title":"The Conformational Cycle of a Prototypical Voltage-Gated Sodium Channel","volume":"16","author":"Catterall","year":"","journal-title":"Nat. Chem. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/s0896-6273(00)80606-6","article-title":"Voltage Sensor-Trapping: Enhanced Activation of Sodium Channels by Beta-Scorpion Toxin Bound to the S3-S4 Loop in Domain II","volume":"21","author":"Cest\u00e8le","year":"1998","journal-title":"Neuron"},{"key":"B22","doi-asserted-by":"publisher","first-page":"11331","DOI":"10.1073\/pnas.1309452110","article-title":"Catalysis of Na+ Permeation in the Bacterial Sodium Channel Na(V)Ab","volume":"110","author":"Chakrabarti","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B23","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1085\/jgp.200308971","article-title":"Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements","volume":"123","author":"Chanda","year":"2004","journal-title":"J. Gen. Physiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1085\/jgp.20028679","article-title":"Tracking Voltage-dependent Conformational Changes in Skeletal Muscle Sodium Channel during Activation","volume":"120","author":"Chanda","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1085\/jgp.117.6.505","article-title":"Interaction of Scorpion Alpha-Toxins with Cardiac Sodium Channels: Binding Properties and Enhancement of Slow Inactivation","volume":"117","author":"Chen","year":"2001","journal-title":"J. Gen. Physiol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav8573","article-title":"Structural Basis of \u03b1-scorpion Toxin Action on Nav Channels","volume":"363","author":"Clairfeuille","year":"2019","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1152\/physrev.00005.2004","article-title":"Inherited and Acquired Vulnerability to Ventricular Arrhythmias: Cardiac Na+ and K+ Channels","volume":"85","author":"Clancy","year":"2005","journal-title":"Physiol. Rev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1093\/cvr\/cvs211","article-title":"Dominant-negative Effect of SCN5A N-Terminal Mutations through the Interaction of Na(v)1.5 \u03b1-subunits","volume":"96","author":"Clatot","year":"2012","journal-title":"Cardiovasc Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1021\/ja210020h","article-title":"Mechanism of Ion Permeation and Selectivity in a Voltage Gated Sodium Channel","volume":"134","author":"Corry","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.10960","article-title":"Binary Architecture of the Nav1.2-\u03b22 Signaling Complex","volume":"5","author":"Das","year":"2016","journal-title":"Elife"},{"key":"B31","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.neuropharm.2017.04.014","article-title":"The Pharmacology of Voltage-Gated Sodium Channel Activators","volume":"127","author":"Deuis","year":"2017","journal-title":"Neuropharmacology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1146\/annurev-neuro-070918-050144","article-title":"Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics","volume":"42","author":"Dib-Hajj","year":"2019","journal-title":"Annu. Rev. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1126\/science.280.5360.69","article-title":"The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity","volume":"280","author":"Doyle","year":"1998","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1007\/BF02257372","article-title":"Classification of Scorpion Toxins According to Amino Acid Composition and Sequence","volume":"20","author":"Dufton","year":"1984","journal-title":"J. Mol. Evol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/0896-6273(94)90312-3","article-title":"Restoration of Inactivation and Block of Open Sodium Channels by an Inactivation Gate Peptide","volume":"12","author":"Eaholtz","year":"1994","journal-title":"Neuron"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3110","DOI":"10.1016\/S0006-3495(96)79505-X","article-title":"On the Structural Basis for Ionic Selectivity Among Na+, K+, and Ca2+ in the Voltage-Gated Sodium Channel","volume":"71","author":"Favre","year":"1996","journal-title":"Biophysical J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"13111","DOI":"10.1073\/pnas.1814928115","article-title":"Fenestrations Control Resting-State Block of a Voltage-Gated Sodium Channel","volume":"115","author":"Gamal El-Din","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B38","doi-asserted-by":"publisher","first-page":"E5016","DOI":"10.1073\/pnas.1314557110","article-title":"Crystallographic Insights into Sodium-Channel Modulation by the \u03b24 Subunit","volume":"110","author":"Gilchrist","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B39","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/s0959-4388(03)00065-5","article-title":"Mechanisms of Sodium Channel Inactivation","volume":"13","author":"Goldin","year":"2003","journal-title":"Curr. Opin. Neurobiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1038\/ncomms2356","article-title":"Multiple Pore Conformations Driven by Asynchronous Movements of Voltage Sensors in a Eukaryotic Sodium Channel","volume":"4","author":"Goldschen-Ohm","year":"2013","journal-title":"Nat. Commun."},{"key":"B41","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1073\/pnas.83.2.508","article-title":"Molecular Model of the Action Potential Sodium Channel","volume":"83","author":"Guy","year":"1986","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1016\/s0021-9258(17)43460-0","article-title":"The Sodium Channel from Rat Brain. Purification and Subunit Composition","volume":"259","author":"Hartshorne","year":"1984","journal-title":"J. Biol. Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1104\/pp.20.00889","article-title":"A Novel Single-Domain Na+-Selective Voltage-Gated Channel in Photosynthetic Eukaryotes","volume":"184","author":"Helliwell","year":"2020","journal-title":"Plant Physiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/j.cub.2019.03.041","article-title":"Alternative Mechanisms for Fast Na+\/Ca2+ Signaling in Eukaryotes via a Novel Class of Single-Domain Voltage-Gated Channels","volume":"29","author":"Helliwell","year":"2019","journal-title":"Curr. Biol."},{"key":"B45","volume-title":"Ionic Channels in Excitable Membranes","author":"Hille","year":"2001"},{"key":"B46","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1085\/jgp.66.5.535","article-title":"Ionic Selectivity, Saturation, and Block in Sodium Channels. A Four-Barrier Model","volume":"66","author":"Hille","year":"1975","journal-title":"J. Gen. Physiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1085\/jgp.69.4.497","article-title":"Local Anesthetics: Hydrophilic and Hydrophobic Pathways for the Drug-Receptor Reaction","volume":"69","author":"Hille","year":"1977","journal-title":"J. Gen. Physiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1073\/pnas.68.2.280","article-title":"The Hydration of Sodium Ions Crossing the Nerve Membrane","volume":"68","author":"Hille","year":"","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B49","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1085\/jgp.59.6.637","article-title":"The Permeability of the Sodium Channel to Metal Cations in Myelinated Nerve","volume":"59","author":"Hille","year":"1972","journal-title":"J. Gen. Physiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1085\/jgp.58.6.599","article-title":"The Permeability of the Sodium Channel to Organic Cations in Myelinated Nerve","volume":"58","author":"Hille","year":"","journal-title":"J. Gen. Physiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1113\/jphysiol.1952.sp004717","article-title":"Currents Carried by Sodium and Potassium Ions through the Membrane of the Giant Axon of Loligo","volume":"116","author":"Hodgkin","year":"","journal-title":"J. Physiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1113\/jphysiol.1952.sp004718","article-title":"The Components of Membrane Conductance in the Giant Axon of Loligo","volume":"116","author":"Hodgkin","year":"","journal-title":"J. Physiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1146\/annurev.pa.24.040184.002131","article-title":"Antiarrhythmic Agents: the Modulated Receptor Mechanism of Action of Sodium and Calcium Channel-Blocking Drugs","volume":"24","author":"Hondeghem","year":"1984","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1111\/jce.14347","article-title":"Update on Antiarrhythmic Drug Pharmacology","volume":"31","author":"Huang","year":"2020","journal-title":"J. Cardiovasc Electrophysiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s13238-017-0372-z","article-title":"Structure-based Assessment of Disease-Related Mutations in Human Voltage-Gated Sodium Channels","volume":"8","author":"Huang","year":"2017","journal-title":"Protein Cell."},{"key":"B56","doi-asserted-by":"publisher","first-page":"457","DOI":"10.2170\/jjphysiol.49.457","article-title":"Point-mutations Related to the Loss of Batrachotoxin Binding Abolish the Grayanotoxin Effect in Na(+) Channel Isoforms","volume":"49","author":"Ishii","year":"1999","journal-title":"Jpn. J. Physiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5260","DOI":"10.1073\/pnas.1010750108","article-title":"Large Shifts in pKa Values of Lysine Residues Buried inside a Protein","volume":"108","author":"Isom","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/0896-6273(94)90436-7","article-title":"Auxiliary Subunits of Voltage-Gated Ion Channels","volume":"12","author":"Isom","year":"1994","journal-title":"Neuron"},{"key":"B59","doi-asserted-by":"publisher","first-page":"5151","DOI":"10.1016\/j.cell.2021.08.021","article-title":"Open-state Structure and Pore Gating Mechanism of the Cardiac Sodium Channel","volume":"184","author":"Jiang","year":"","journal-title":"Cell."},{"key":"B60","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/bs.mie.2021.01.030","article-title":"Expression and Purification of the Cardiac Sodium Channel NaV1.5 for Cryo-EM Structure Determination","volume":"653","author":"Jiang","year":"","journal-title":"Methods Enzymol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/s41586-018-0120-4","article-title":"Structural Basis for Gating Pore Current in Periodic Paralysis","volume":"557","author":"Jiang","year":"2018","journal-title":"Nature"},{"key":"B62","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.cell.2019.11.041","article-title":"Structure of the Cardiac Sodium Channel","volume":"180","author":"Jiang","year":"2020","journal-title":"Cell."},{"key":"B63","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/s41467-020-20078-3","article-title":"Structural Basis for Voltage-Sensor Trapping of the Cardiac Sodium Channel by a Deathstalker Scorpion Toxin","volume":"12","author":"Jiang","year":"","journal-title":"Nat. Commun."},{"key":"B64","first-page":"997","article-title":"Tetrodotoxin, Saxitoxin and Their Significance in the Study of Excitation Phenomena","volume":"18","author":"Kao","year":"1966","journal-title":"Pharmacol. Rev."},{"key":"B65","doi-asserted-by":"publisher","first-page":"30971","DOI":"10.1074\/jbc.271.48.30971","article-title":"Movement of the Na+ Channel Inactivation Gate during Inactivation","volume":"271","author":"Kellenberger","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-019-00065-0","article-title":"Nav1.7 Withholds its Pain Potential","author":"Kingwell","year":"2019","journal-title":"Nat. Rev. Drug Discov"},{"key":"B67","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/BF01870449","article-title":"Block of Single Cardiac Na+ Channels by Antiarrhythmic Drugs: the Effect of Amiodarone, Propafenone and Diprafenone","volume":"102","author":"Kohlhardt","year":"1988","journal-title":"J. Membr. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"9532","DOI":"10.1074\/jbc.M313100200","article-title":"A Superfamily of Voltage-Gated Sodium Channels in Bacteria","volume":"279","author":"Koishi","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B69","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1111\/j.1432-1033.1974.tb03716.x","article-title":"Disulfide Bonds of Toxin II of the Scorpion Androctonus Australis Hector","volume":"47","author":"Kopeyan","year":"1974","journal-title":"Eur. J. Biochem."},{"key":"B70","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1001\/archinte.158.4.325","article-title":"Pharmacological Effects of Antiarrhythmic Drugs. Review and Update","volume":"158","author":"Kowey","year":"1998","journal-title":"Arch. Intern Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/j.1749-6632.1986.tb15571.x","article-title":"Polypeptide Toxins as Tools to Study Voltage-Sensitive Na+ Channels","volume":"479","author":"Lazdunski","year":"1986","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"E3051","DOI":"10.1073\/pnas.1700761114","article-title":"Structures of Closed and Open States of a Voltage-Gated Sodium Channel","volume":"114","author":"Lenaeus","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B73","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1111\/j.1469-7793.1997.345bb.x","article-title":"Role in Fast Inactivation of the IV\/S4-S5 Loop of the Human Muscle Na+ Channel Probed by Cysteine Mutagenesis","author":"Lerche","year":"1997","journal-title":"J. Physiol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1038\/s41467-022-28808-5","article-title":"Structural Basis for Modulation of Human NaV1.3 by Clinical Drug and Selective Antagonist","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"B75","doi-asserted-by":"publisher","first-page":"11474","DOI":"10.1002\/anie.202102196","article-title":"Structural Basis for Pore Blockade of the Human Cardiac Sodium Channel Nav 1.5 by the Antiarrhythmic Drug Quinidine*","volume":"60","author":"Li","year":"","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2100069118","article-title":"Structure of Human Na V 1.5 Reveals the Fast Inactivation-Related Segments as a Mutational Hotspot for the Long QT Syndrome","volume":"118","author":"Li","year":"","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B77","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1085\/jgp.20028723","article-title":"Common Molecular Determinants of Flecainide and Lidocaine Block of Heart Na+ Channels: Evidence from Experiments with Neutral and Quaternary Flecainide Analogues","volume":"121","author":"Liu","year":"2003","journal-title":"J. Gen. Physiol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1126\/science.1116269","article-title":"Crystal Structure of a Mammalian Voltage-dependent Shaker Family K+ Channel","volume":"309","author":"Long","year":"2005","journal-title":"Science"},{"key":"B79","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1172\/JCI34057","article-title":"The E1784K Mutation in SCN5A Is Associated with Mixed Clinical Phenotype of Type 3 Long QT Syndrome","volume":"118","author":"Makita","year":"2008","journal-title":"J. Clin. Invest."},{"key":"B80","doi-asserted-by":"publisher","first-page":"7571","DOI":"10.1016\/s0021-9258(17)37325-8","article-title":"Voltage-gated Na+ Channel Beta 1 Subunit mRNA Expressed in Adult Human Skeletal Muscle, Heart, and Brain Is Encoded by a Single Gene","volume":"269","author":"Makita","year":"1994","journal-title":"J. Biol. Chem."},{"key":"B81","doi-asserted-by":"publisher","first-page":"4495","DOI":"10.1073\/pnas.1720185115","article-title":"Spider Toxin Inhibits Gating Pore Currents Underlying Periodic Paralysis","volume":"115","author":"M\u00e4nnikk\u00f6","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B82","doi-asserted-by":"publisher","first-page":"15348","DOI":"10.1073\/pnas.211563298","article-title":"Role of the C-Terminal Domain in Inactivation of Brain and Cardiac Sodium Channels","volume":"98","author":"Mantegazza","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B83","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1161\/01.res.80.3.363","article-title":"Effects of Tityus Serrulatus Scorpion Toxin Gamma on Voltage-Gated Na+ Channels","volume":"80","author":"Marcotte","year":"1997","journal-title":"Circ. Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/0041-0101(87)90293-5","article-title":"Use of High Performance Liquid Chromatography to Demonstrate Quantitative Variation in Components of Venom from the Scorpion Androctonus Australis Hector","volume":"25","author":"Martin","year":"1987","journal-title":"Toxicon"},{"key":"B85","doi-asserted-by":"publisher","first-page":"E2724","DOI":"10.1073\/pnas.1220844110","article-title":"Voltage Sensor Interaction Site for Selective Small Molecule Inhibitors of Voltage-Gated Sodium Channels","volume":"110","author":"McCormack","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1097\/j.pain.0000000000001227","article-title":"Efficacy of the Nav1.7 Blocker PF-05089771 in a Randomised, Placebo-Controlled, Double-Blind Clinical Study in Subjects with Painful Diabetic Peripheral Neuropathy","volume":"159","author":"McDonnell","year":"2018","journal-title":"Pain"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1074\/jbc.273.2.1121","article-title":"A Critical Role for the S4-S5 Intracellular Loop in Domain IV of the Sodium Channel Alpha-Subunit in Fast Inactivation","volume":"273","author":"McPhee","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B88","doi-asserted-by":"publisher","first-page":"12346","DOI":"10.1073\/pnas.91.25.12346","article-title":"A Mutation in Segment IVS6 Disrupts Fast Inactivation of Sodium Channels","volume":"91","author":"McPhee","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B89","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1172\/JCI25466","article-title":"Sodium Channel Mutations in Epilepsy and Other Neurological Disorders","volume":"115","author":"Meisler","year":"2005","journal-title":"J. Clin. Invest."},{"key":"B90","doi-asserted-by":"publisher","first-page":"14734","DOI":"10.1021\/bi026546a","article-title":"Two Tarantula Peptides Inhibit Activation of Multiple Sodium Channels","volume":"41","author":"Middleton","year":"2002","journal-title":"Biochemistry"},{"key":"B91","doi-asserted-by":"publisher","first-page":"10797","DOI":"10.1074\/jbc.M113.527994","article-title":"Crystal Structure and Molecular Imaging of the Nav Channel \u03b23 Subunit Indicates a Trimeric Assembly","volume":"289","author":"Namadurai","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B92","doi-asserted-by":"publisher","first-page":"140192","DOI":"10.1098\/rsob.140192","article-title":"A New Look at Sodium Channel \u03b2 Subunits","volume":"5","author":"Namadurai","year":"2015","journal-title":"Open Biol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"820","DOI":"10.15252\/embj.201593285","article-title":"Molecular Basis of Ion Permeability in a Voltage-Gated Sodium Channel","volume":"35","author":"Naylor","year":"2016","journal-title":"EMBO J."},{"key":"B94","doi-asserted-by":"publisher","first-page":"2945","DOI":"10.1073\/pnas.1817446116","article-title":"Structural Basis for Antiarrhythmic Drug Interactions with the Human Cardiac Sodium Channel","volume":"116","author":"Nguyen","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B95","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/312121a0","article-title":"Primary Structure of Electrophorus Electricus Sodium Channel Deduced from cDNA Sequence","volume":"312","author":"Noda","year":"1984","journal-title":"Nature"},{"key":"B96","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/0014-5793(89)81531-5","article-title":"A Single Point Mutation Confers Tetrodotoxin and Saxitoxin Insensitivity on the Sodium Channel II","volume":"259","author":"Noda","year":"1989","journal-title":"FEBS Lett."},{"key":"B97","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3389\/fgene.2013.00213","article-title":"Sodium Channel SCN8A (Nav1.6): Properties and De Novo Mutations in Epileptic Encephalopathy and Intellectual Disability","volume":"4","author":"O'Brien","year":"2013","journal-title":"Front. Genet."},{"key":"B98","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1146\/annurev-physiol-021014-071846","article-title":"Sodium Channel \u03b2 Subunits: Emerging Targets in Channelopathies","volume":"77","author":"O'Malley","year":"2015","journal-title":"Annu. Rev. Physiol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1093\/cvr\/cvq348","article-title":"Mutations in Sodium Channel \u03b2-subunit SCN3B Are Associated with Early-Onset Lone Atrial Fibrillation","volume":"89","author":"Olesen","year":"2011","journal-title":"Cardiovasc Res."},{"key":"B100","doi-asserted-by":"publisher","first-page":"14791","DOI":"10.1038\/s41598-020-71135-2","article-title":"Discovery of a Selective, State-independent Inhibitor of NaV1.7 by Modification of Guanidinium Toxins","volume":"10","author":"Pajouhesh","year":"2020","journal-title":"Sci. Rep."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1126\/science.aaw2999","article-title":"Molecular Basis for Pore Blockade of Human Na+ Channel Nav1.2 by the \u03bc-conotoxin KIIIA","volume":"363","author":"Pan","year":"2019","journal-title":"Science"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau2486","article-title":"Structure of the Human Voltage-Gated Sodium Channel Nav1.4 in Complex with \u03b21","volume":"362","author":"Pan","year":"2018","journal-title":"Science"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2100066118","article-title":"Comparative Structural Analysis of Human Na V 1.1 and Na V 1.5 Reveals Mutational Hotspots for Sodium Channelopathies","volume":"118","author":"Pan","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B104","doi-asserted-by":"publisher","first-page":"14577","DOI":"10.1523\/JNEUROSCI.0361-11.2011","article-title":"Voltage-gated Na+ Channel \u03b21B: a Secreted Cell Adhesion Molecule Involved in Human Epilepsy","volume":"31","author":"Patino","year":"2011","journal-title":"J. Neurosci."},{"key":"B105","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/nature11077","article-title":"Crystal Structure of a Voltage-Gated Sodium Channel in Two Potentially Inactivated States","volume":"486","author":"Payandeh","year":"2012","journal-title":"Nature"},{"key":"B106","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nature10238","article-title":"The Crystal Structure of a Voltage-Gated Sodium Channel","volume":"475","author":"Payandeh","year":"2011","journal-title":"Nature"},{"key":"B107","doi-asserted-by":"publisher","first-page":"47564","DOI":"10.1074\/jbc.M204063200","article-title":"Function and Solution Structure of Huwentoxin-IV, a Potent Neuronal Tetrodotoxin (TTX)-sensitive Sodium Channel Antagonist from Chinese Bird Spider Selenocosmia Huwena","volume":"277","author":"Peng","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B108","doi-asserted-by":"publisher","first-page":"778534","DOI":"10.3389\/fphar.2021.778534","article-title":"A Novel Spider Toxin Inhibits Fast Inactivation of the Nav1.9 Channel by Binding to Domain III and Domain IV Voltage Sensors","volume":"12","author":"Peng","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"25696","DOI":"10.1074\/jbc.270.43.25696","article-title":"Modulation of Cardiac Na+ Channel Expression in Xenopus Oocytes by Beta 1 Subunits","volume":"270","author":"Qu","year":"1995","journal-title":"J. Biol. Chem."},{"key":"B110","doi-asserted-by":"publisher","first-page":"6732","DOI":"10.1073\/pnas.79.21.6732","article-title":"Modification of Single Na+ Channels by Batrachotoxin","volume":"79","author":"Quandt","year":"1982","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B111","doi-asserted-by":"publisher","first-page":"9270","DOI":"10.1073\/pnas.93.17.9270","article-title":"Common Molecular Determinants of Local Anesthetic, Antiarrhythmic, and Anticonvulsant Block of Voltage-Gated Na+ Channels","volume":"93","author":"Ragsdale","year":"1996","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1126\/science.8085162","article-title":"Molecular Determinants of State-dependent Block of Na+ Channels by Local Anesthetics","volume":"265","author":"Ragsdale","year":"1994","journal-title":"Science"},{"key":"B113","doi-asserted-by":"publisher","first-page":"e0173551","DOI":"10.1371\/journal.pone.0173551","article-title":"The Structure, Dynamics and Selectivity Profile of a NaV1.7 Potency-Optimised Huwentoxin-IV Variant","volume":"12","author":"Rahnama","year":"2017","journal-title":"PLoS One"},{"key":"B114","doi-asserted-by":"publisher","first-page":"4517","DOI":"10.1523\/jneurosci.17-12-04517.1997","article-title":"Resurgent Sodium Current and Action Potential Formation in Dissociated Cerebellar Purkinje Neurons","volume":"17","author":"Raman","year":"1997","journal-title":"J. Neurosci."},{"key":"B115","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/s0896-6273(00)80969-1","article-title":"Altered Subthreshold Sodium Currents and Disrupted Firing Patterns in Purkinje Neurons of Scn8a Mutant Mice","volume":"19","author":"Raman","year":"1997","journal-title":"Neuron"},{"key":"B116","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1126\/science.1065635","article-title":"A Prokaryotic Voltage-Gated Sodium Channel","volume":"294","author":"Ren","year":"2001","journal-title":"Science"},{"key":"B117","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.peptides.2013.03.011","article-title":"Potency Optimization of Huwentoxin-IV on hNav1.7: a Neurotoxin TTX-S Sodium-Channel Antagonist from the Venom of the Chinese Bird-Eating Spider Selenocosmia Huwena","volume":"44","author":"Revell","year":"2013","journal-title":"Peptides"},{"key":"B118","first-page":"325","article-title":"Scorpion Toxins: Chemistry and Mode of Action","volume":"3","author":"Rochat","year":"1979","journal-title":"Adv. Cytopharmacol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"15950","DOI":"10.1074\/jbc.271.27.15950","article-title":"Molecular Determinants of High Affinity Binding of Alpha-Scorpion Toxin and Sea Anemone Toxin in the S3-S4 Extracellular Loop in Domain IV of the Na+ Channel Alpha Subunit","volume":"271","author":"Rogers","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B120","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1021\/bi9823380","article-title":"Solution Structure of the Sodium Channel Inactivation Gate","volume":"38","author":"Rohl","year":"1999","journal-title":"Biochemistry"},{"key":"B121","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1007\/s40261-019-00807-3","article-title":"Safety, Tolerability, and Pharmacokinetics of GDC-0276, a Novel NaV1.7 Inhibitor, in a First-In-Human, Single- and Multiple-Dose Study in Healthy Volunteers","volume":"39","author":"Rothenberg","year":"2019","journal-title":"Clin. Drug Investig."},{"key":"B122","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nrcardio.2009.44","article-title":"Sodium Channel Mutations and Arrhythmias","volume":"6","author":"Ruan","year":"2009","journal-title":"Nat. Rev. Cardiol."},{"key":"B123","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1038\/35059098","article-title":"The Voltage-Sensitive Sodium Channel Is a Bell-Shaped Molecule with Several Cavities","volume":"409","author":"Sato","year":"2001","journal-title":"Nature"},{"key":"B124","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.semcdb.2010.10.002","article-title":"Regulation of Sodium Channel Activity by Phosphorylation","volume":"22","author":"Scheuer","year":"2011","journal-title":"Semin. Cell. Dev. Biol."},{"key":"B125","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1124\/mol.108.047670","article-title":"ProTx-II, a Selective Inhibitor of NaV1.7 Sodium Channels, Blocks Action Potential Propagation in Nociceptors","volume":"74","author":"Schmalhofer","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau2596","article-title":"Structural Basis for the Modulation of Voltage-Gated Sodium Channels by Animal Toxins","volume":"362","author":"Shen","year":"2018","journal-title":"Science"},{"key":"B127","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1126\/science.aaw2493","article-title":"Structures of Human Nav1.7 Channel in Complex with Auxiliary Subunits and Animal Toxins","volume":"363","author":"Shen","year":"2019","journal-title":"Science"},{"key":"B128","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/bs.mie.2021.03.010","article-title":"Structural Determination of Human Nav1.4 and Nav1.7 Using Single Particle Cryo-Electron Microscopy","volume":"653","author":"Shen","year":"2021","journal-title":"Methods Enzymol."},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal4326","article-title":"Structure of a Eukaryotic Voltage-Gated Sodium Channel at Near-Atomic Resolution","volume":"355","author":"Shen","year":"2017","journal-title":"Science"},{"key":"B130","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/s0014-5793(97)00479-1","article-title":"A Single Serine Residue Confers Tetrodotoxin Insensitivity on the Rat Sensory-neuron-specific Sodium Channel SNS","volume":"409","author":"Sivilotti","year":"1997","journal-title":"FEBS Lett."},{"key":"B131","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1016\/S0006-3495(97)78219-5","article-title":"Interaction between the Sodium Channel Inactivation Linker and Domain III S4-S5","volume":"73","author":"Smith","year":"1997","journal-title":"Biophys. J."},{"key":"B132","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1124\/mol.107.041046","article-title":"Inhibition of Sodium Channel Gating by Trapping the Domain II Voltage Sensor with Protoxin II","volume":"73","author":"Sokolov","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/nature05598","article-title":"Gating Pore Current in an Inherited Ion Channelopathy","volume":"446","author":"Sokolov","year":"2007","journal-title":"Nature"},{"key":"B134","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/339597a0","article-title":"Structural Parts Involved in Activation and Inactivation of the Sodium Channel","volume":"339","author":"St\u00fchmer","year":"1989","journal-title":"Nature"},{"key":"B135","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/BF00253837","article-title":"Patch Clamp Characterization of Sodium Channels Expressed from Rat Brain cDNA","volume":"14","author":"St\u00fchmer","year":"1987","journal-title":"Eur. Biophys. J."},{"key":"B136","doi-asserted-by":"publisher","first-page":"14205","DOI":"10.1038\/ncomms14205","article-title":"The Complete Structure of an Activated Open Sodium Channel","volume":"8","author":"Sula","year":"2017","journal-title":"Nat. Commun."},{"key":"B137","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1085\/jgp.110.6.693","article-title":"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","volume":"110","author":"Sun","year":"1997","journal-title":"J. Gen. Physiol."},{"key":"B138","doi-asserted-by":"publisher","first-page":"2326","DOI":"10.1073\/pnas.030438797","article-title":"A Critical Residue for Isoform Difference in Tetrodotoxin Affinity Is a Molecular Determinant of the External Access Path for Local Anesthetics in the Cardiac Sodium Channel","volume":"97","author":"Sunami","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B139","doi-asserted-by":"publisher","first-page":"11457","DOI":"10.1016\/s0021-9258(19)68422-x","article-title":"Reconstitution of the Voltage-Sensitive Sodium Channel of Rat Brain from Solubilized Components","volume":"256","author":"Tamkun","year":"1981","journal-title":"J. Biol. Chem."},{"key":"B140","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature12775","article-title":"Structural Basis for Ca2+ Selectivity of a Voltage-Gated Calcium Channel","volume":"505","author":"Tang","year":"2014","journal-title":"Nature"},{"key":"B141","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/nature19102","article-title":"Structural Basis for Inhibition of a Voltage-Gated Ca2+ Channel by Ca2+ Antagonist Drugs","volume":"537","author":"Tang","year":"2016","journal-title":"Nature"},{"key":"B142","first-page":"886","article-title":"Studies on the Analgesic Action and Physical Dependence of Bulleyaconitine A","volume":"21","author":"Tang","year":"1986","journal-title":"Yao Xue Xue Bao"},{"key":"B143","doi-asserted-by":"publisher","first-page":"10161","DOI":"10.1073\/pnas.86.24.10161","article-title":"Localization of the Receptor Site for Alpha-Scorpion Toxins by Antibody Mapping: Implications for Sodium Channel Topology","volume":"86","author":"Thomsen","year":"1989","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B144","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/BFb0111446","article-title":"The Effect of Veratridine on Excitable Membranes of Nerve and Muscle","volume":"61","author":"Ulbricht","year":"1969","journal-title":"Ergeb Physiol."},{"key":"B145","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1126\/science.241.4873.1658","article-title":"Identification of an Intracellular Peptide Segment Involved in Sodium Channel Inactivation","volume":"241","author":"Vassilev","year":"1988","journal-title":"Science"},{"key":"B146","doi-asserted-by":"publisher","first-page":"7909","DOI":"10.1523\/jneurosci.21-20-07909.2001","article-title":"Gating Properties of Na(v)1.7 and Na(v)1.8 Peripheral Nerve Sodium Channels","volume":"21","author":"Vijayaragavan","year":"2001","journal-title":"J. Neurosci."},{"key":"B147","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1097\/01.anes.0000267502.18605.ad","article-title":"Bulleyaconitine A Isolated from Aconitum Plant Displays Long-Acting Local Anesthetic Properties In Vitro and In Vivo","volume":"107","author":"Wang","year":"2007","journal-title":"Anesthesiology"},{"key":"B148","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1007\/s004249900229","article-title":"Modification of Wild-type and Batrachotoxin-Resistant Muscle Mu1 Na+ Channels by Veratridine","volume":"439","author":"Wang","year":"2000","journal-title":"Pflugers Arch."},{"key":"B149","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1085\/jgp.200308857","article-title":"State-dependent Block of Wild-type and Inactivation-Deficient Na+ Channels by Flecainide","volume":"122","author":"Wang","year":"2003","journal-title":"J. Gen. Physiol."},{"key":"B150","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1124\/mol.59.5.1100","article-title":"Disparate Role of Na(+) Channel D2-S6 Residues in Batrachotoxin and Local Anesthetic Action","volume":"59","author":"Wang","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"B151","doi-asserted-by":"publisher","first-page":"3141","DOI":"10.1016\/S0006-3495(99)77465-5","article-title":"Batrachotoxin-resistant Na+ Channels Derived from Point Mutations in Transmembrane Segment D4-S6","volume":"76","author":"Wang","year":"1999","journal-title":"Biophys. J."},{"key":"B152","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1073\/pnas.95.5.2653","article-title":"Point Mutations in Segment I-S6 Render Voltage-Gated Na+ Channels Resistant to Batrachotoxin","volume":"95","author":"Wang","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B153","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1161\/CIRCEP.108.779181","article-title":"Mutations in Sodium Channel \u03b21- and \u03b22-subunits Associated with Atrial Fibrillation","volume":"2","author":"Watanabe","year":"2009","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"B154","doi-asserted-by":"publisher","first-page":"3651","DOI":"10.1073\/pnas.79.11.3651","article-title":"Functional Reconstitution of the Purified Sodium Channel Protein from Rat Sarcolemma","volume":"79","author":"Weigele","year":"1982","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B155","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nature09975","article-title":"Loss-of-function Mutations in Sodium Channel Nav1.7 Cause Anosmia","volume":"472","author":"Weiss","year":"2011","journal-title":"Nature"},{"key":"B156","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1126\/science.1658937","article-title":"A Phosphorylation Site in the Na+ Channel Required for Modulation by Protein Kinase C","volume":"254","author":"West","year":"1991","journal-title":"Science"},{"key":"B157","doi-asserted-by":"publisher","first-page":"10910","DOI":"10.1073\/pnas.89.22.10910","article-title":"A Cluster of Hydrophobic Amino Acid Residues Required for Fast Na(+)-Channel Inactivation","volume":"89","author":"West","year":"1992","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B158","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.molcel.2020.10.039","article-title":"Structural Basis for High-Affinity Trapping of the NaV1.7 Channel in its Resting State by Tarantula Toxin","volume":"81","author":"Wisedchaisri","year":"2021","journal-title":"Mol. Cell."},{"key":"B159","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/j.cell.2019.06.031","article-title":"Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel","volume":"178","author":"Wisedchaisri","year":"2019","journal-title":"Cell."},{"key":"B160","doi-asserted-by":"publisher","first-page":"27300","DOI":"10.1074\/jbc.M708447200","article-title":"Tarantula Huwentoxin-IV Inhibits Neuronal Sodium Channels by Binding to Receptor Site 4 and Trapping the Domain Ii Voltage Sensor in the Closed Configuration","volume":"283","author":"Xiao","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B161","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1124\/mol.110.066332","article-title":"The Tarantula Toxins ProTx-II and Huwentoxin-IV Differentially Interact with Human Nav1.7 Voltage Sensors to Inhibit Channel Activation and Inactivation","volume":"78","author":"Xiao","year":"2010","journal-title":"Mol. Pharmacol."},{"key":"B162","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.cell.2019.01.047","article-title":"Structural Basis of Nav1.7 Inhibition by a Gating-Modifier Spider Toxin","volume":"176","author":"Xu","year":"2019","journal-title":"Cell."},{"key":"B163","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.cell.2017.06.039","article-title":"Structure of the Nav1.4-\u03b21 Complex from Electric Eel","volume":"170","author":"Yan","year":"2017","journal-title":"Cell."},{"key":"B164","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nature00978","article-title":"The Voltage-Gated Potassium Channels and Their Relatives","volume":"419","author":"Yellen","year":"2002","journal-title":"Nature"},{"key":"B165","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1085\/jgp.20028699","article-title":"The Cation Selectivity Filter of the Bacterial Sodium Channel, NaChBac","volume":"120","author":"Yue","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"B166","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1038\/nature11054","article-title":"Crystal Structure of an Orthologue of the NaChBac Voltage-Gated Sodium Channel","volume":"486","author":"Zhang","year":"2012","journal-title":"Nature"},{"key":"B167","doi-asserted-by":"publisher","first-page":"962","DOI":"10.2174\/156802612800229206","article-title":"Sodium Channel Blockers as Therapeutic Target for Treating Epilepsy: Recent Updates","volume":"12","author":"Zuliani","year":"2012","journal-title":"Curr. Top. Med. Chem."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.908867\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T03:52:29Z","timestamp":1654228349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.908867\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,3]]},"references-count":167,"alternative-id":["10.3389\/fphar.2022.908867"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.908867","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,3]]},"article-number":"908867"}}