Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology

References

• Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952;117(4):500–23. doi: 10.1113/jphysiol.1952.sp004764
   PubMed Web of Science ®Google Scholar
• Hall AE, Hutter OF, Noble D. Current-voltage relations of Purkinje fibres in sodium-deficient solutions. J Physiol. 1963;166:2225–2240. doi: 10.1113/jphysiol.1963.sp007102
   Web of Science ®Google Scholar
• Adrian RH, Chandler WK, Hodgkin AL. Voltage clamp experiments in striated muscle fibres. J Physiol. 1970;208(3):607–644. doi: 10.1113/jphysiol.1970.sp009139
   PubMed Web of Science ®Google Scholar
• Hille B. Ionic channels of excitable membranes. 3rd ed. Sunderland (MA): Sinauer Associates Inc.; 2001.
   Google Scholar
• Eckert R, Brehm P. Ionic mechanisms of excitation in Paramecium. Annu Rev Biophys Bioeng. 1979;8(1):353–383. doi: 10.1146/annurev.bb.08.060179.002033
   PubMedGoogle Scholar
• Ashcroft FM, Stanfield PR. Calcium and potassium currents in muscle fibres of an insect (carausius morosus). J Physiol. 1982;323(1):93–115. doi: 10.1113/jphysiol.1982.sp014063
   PubMedGoogle Scholar
• Torrente AG, Mesirca P, Bidaud I, et al. Channelopathies of voltage-gated L-type Cav1.3 channels. Pflugers Arch. 2020;472(7):817–830. doi: 10.1007/s00424-020-02421-1
   PubMed Web of Science ®Google Scholar
• Perez-Reyes E. Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev. 2003;83(1):117–161. doi: 10.1152/physrev.00018.2002
   PubMed Web of Science ®Google Scholar
• Deleuze C, David F, Behuret S, et al. T-type calcium channels consolidate tonic action potential output of thalamic neurons to neocortex. J Neurosci. 2012;32(35):12228–12236. doi: 10.1523/JNEUROSCI.1362-12.2012
   PubMed Web of Science ®Google Scholar
• Reuter H. The dependence of slow inward current in Purkinje fibres on the extracellular calcium-concentration. J Physiol (Lond). 1967;192(2):479–492. doi: 10.1113/jphysiol.1967.sp008310
   Google Scholar
• Reuter H. Properties of two inward membrane currents in the heart. Annu Rev Physiol. 1979;41(1):413–424. doi: 10.1146/annurev.ph.41.030179.002213
   PubMedGoogle Scholar
• Brehm P, Eckert R. Calcium entry leads to inactivation of calcium channel in Paramecium Science. Science. 1978;202(4373):1203–1206. doi: 10.1126/science.103199
   PubMed Web of Science ®Google Scholar
• Tsien RW, Elinor PT, Horne WA. Molecular diversity of voltage-dependent calcium channels. Trends Neurosci. 1991;12:349–354. doi: 10.1016/0165-6147(91)90595-J
   Google Scholar
• Catterall WA. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Annu Rev Pharmacol Toxicol. 1980;20(1):15–43. doi: 10.1146/annurev.pa.20.040180.000311
   PubMedGoogle Scholar
• Olivera BM, Miljanich GP, Ramachandran J, et al. Calcium channel diversity and neurotransmitter release: The omega-conotoxins and omega-agatoxins. Annu Rev Biochem. 1994;63:823–867. doi: 10.1146/annurev.bi.63.070194.004135
   PubMed Web of Science ®Google Scholar
• Beneski DA, Catterall WA. Covalent labeling of protein components of the sodium channel with a photoactivable derivative of scorpion toxin. Proc Natl Acad Sci, USA. 1980;77(1):639–643. doi: 10.1073/pnas.77.1.639
   PubMed Web of Science ®Google Scholar
• Hartshorne RP, Coppersmith J, Catterall WA. Size characteristics of the solubilized saxitoxin receptor of the voltage-sensitive sodium channel from rat brain. J Biol Chem. 1981;255:10572–10575. doi: 10.1016/S0021-9258(19)70342-1
   Web of Science ®Google Scholar
• Hartshorne RP, Catterall WA. Purification of the saxitoxin receptor of the sodium channel from rat brain. Proc Natl Acad Sci, USA. 1981;78(7):4620–4624. doi: 10.1073/pnas.78.7.4620
   PubMed Web of Science ®Google Scholar
• Hartshorne RP, Messner DJ, Coppersmith JC, et al. The saxitoxin receptor of the sodium channel from rat brain evidence for two nonidentical beta subunits. J Biol Chem. 1982;257:13888–13891. doi: 10.1016/S0021-9258(19)45312-X
   PubMed Web of Science ®Google Scholar
• Hartshorne RP, Catterall WA. The sodium channel from rat brain. Purification and subunit composition. J Biol Chem. 1984;259(3):1667–1675. doi: 10.1016/S0021-9258(17)43460-0
   PubMed Web of Science ®Google Scholar
• Talvenheimo JA, Tamkun MM, Catterall WA. Reconstitution of neurotoxin-stimulated sodium transport by the voltage-sensitive sodium channel purified from rat brain. J Biol Chem. 1982;257(20):11868–11871. doi: 10.1016/S0021-9258(18)33644-5
   PubMed Web of Science ®Google Scholar
• Tamkun MM, Talvenheimo JA, Catterall WA. The sodium channel from rat brain. Reconstitution of neurotoxin-activated ion flux and scorpion toxin binding from purified components. J Biol Chem. 1984;259(3):1676–1688. doi: 10.1016/S0021-9258(17)43461-2
   PubMed Web of Science ®Google Scholar
• Hartshorne RP, Keller BU, Talvenheimo JA, et al. Functional reconstitution of the purified brain sodium channel in planar lipid bilayers. Proc Natl Acad Sci, USA. 1985;82(1):240–244. doi: 10.1073/pnas.82.1.240
   PubMed Web of Science ®Google Scholar
• Agnew WS, Moore AC, Levinson SR, et al. Identification of a large molecular weight peptide associated with a tetrodotoxin binding proteins from the electroplax of electrophorus electricus. Biochem Biophys Res Commun. 1980;92:860–866. doi: 10.1016/0006-291X(80)90782-2
   PubMed Web of Science ®Google Scholar
• Miller JA, Agnew WS, Levinson SR. Principal glycopeptide of the tetrodotoxin/saxitoxin binding protein from electrophorus electricus: isolation and partial chemical and physical characterization. Biochemistry. 1983;22:462–470. doi: 10.1021/bi00271a032
   PubMed Web of Science ®Google Scholar
• Barchi RL. Protein components of the purified sodium channel from rat skeletal sarcolemma. J Neurochem. 1983;36:1377–1385. doi: 10.1111/j.1471-4159.1983.tb13580.x
   Google Scholar
• Catterall WA. The molecular basis of neuronal excitability. Science. 1984;223(4637):653–661. doi: 10.1126/science.6320365
   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;312(5990):121–127. doi: 10.1038/312121a0
   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;320(6058):188–192. doi: 10.1038/320188a0
   PubMed Web of Science ®Google Scholar
• Goldin AL, Snutch T, Lubbert H, et al. Messenger RNA coding for only the α subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes. Proc Natl Acad Sci, USA. 1986;83:7503–7507. doi: 10.1073/pnas.83.19.7503
   PubMed Web of Science ®Google Scholar
• Auld VJ, Goldin AL, Krafte DS, et al. A rat brain sodium channel α subunit with novel gating properties. Neuron. 1988;1:449–461. doi: 10.1016/0896-6273(88)90176-6
   PubMed Web of Science ®Google Scholar
• Trimmer JS, Cooperman SS, Tomiko SA, et al. Primary structure and functional expression of a mammalian skeletal muscle sodium channel. Neuron. 1989;3(1):33–49. doi: 10.1016/0896-6273(89)90113-X
   PubMed Web of Science ®Google Scholar
• Rogart RB, Cribbs LL, Muglia LK, et al. Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform. Proc Natl Acad Sci, USA. 1989;86(20):8170–8174. doi: 10.1073/pnas.86.20.8170
   PubMed Web of Science ®Google Scholar
• Catterall WA. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron. 2000;26(1):13–25. doi: 10.1016/S0896-6273(00)81133-2
   PubMed Web of Science ®Google Scholar
• Bezanilla F. The voltage sensor in voltage-dependent ion channels. Physiol Rev. 2000;80(2):555–592. doi: 10.1152/physrev.2000.80.2.555
   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;147(1):1–24. doi: 10.1085/jgp.201511492
   PubMed Web of Science ®Google Scholar
• Isom LL, De Jongh KS, Patton DE, et al. Primary structure and functional expression of the β1 subunit of the rat brain sodium channel. Science. 1992;256(5058):839–842. doi: 10.1126/science.256.5058.839
   PubMed Web of Science ®Google Scholar
• Isom LL, Ragsdale DS, De Jongh KS, et al. Structure and function of the β2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell. 1995;83(3):433–442. doi: 10.1016/0092-8674(95)90121-3
   PubMed Web of Science ®Google Scholar
• Isom LL, Catterall WA. Na+ channel subunits and Igg domains. Nature. 1996;383(6598):307–308. doi: 10.1038/383307b0
   PubMed Web of Science ®Google Scholar
• Morgan K, Stevens EB, Shah B, et al. Beta-3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics. Proc Natl Acad Sci, USA. 2000;97(5):2308–2313. doi: 10.1073/pnas.030362197
   PubMed Web of Science ®Google Scholar
• Yu FH, Westenbroek RE, Silos-Santiago I, et al. Sodium channel beta-4, a new disulfide-linked auxiliary subunit with similarity to beta-2. J Neurosci. 2003;23(20):7577–7585. doi: 10.1523/JNEUROSCI.23-20-07577.2003
   PubMed Web of Science ®Google Scholar
• Murphy KMM, Gould RJ, Largent BL, et al. A unitary mechanism of calcium antagonist drug action. Proc Natl Acad Sci, USA. 1983;80(3):860–864. doi: 10.1073/pnas.80.3.860
   PubMed Web of Science ®Google Scholar
• Glossmann H, Ferry R, Goll A, et al. Calcium channels: basic properties as revealed by radioligand binding studies. J Cardiovasc Pharmacol. 1985;7:520–530. doi: 10.1097/00005344-198500076-00005
   PubMed Web of Science ®Google Scholar
• Curtis BM, Catterall WA. Purification of the calcium antagonist receptor of the voltage-sensitive calcium channel from skeletal muscle transverse tubules. Biochem. 1984;23(10):2113–2118. doi: 10.1021/bi00305a001
   PubMed Web of Science ®Google Scholar
• Curtis BM, Catterall WA. Reconstitution of the voltage-sensitive calcium channel purified from skeletal muscle transverse tubules. Biochemistry. 1986;25(11):3077–3083. doi: 10.1021/bi00359a002
   PubMed Web of Science ®Google Scholar
• Sieber M, Nastainczyk W, Zubor V, et al. The 165-kDa peptide of the purified skeletal muscle dihydropyridine receptor contains the known regulatory sites of the calcium channel. Eur J Biochem. 1987;167(1):117–122. doi: 10.1111/j.1432-1033.1987.tb13311.x
   PubMedGoogle Scholar
• Flockerzi V, Oeken HJ, Hofmann F, et al. Purified dihydropyridine-binding site from skeletal muscle t-tubules is a functional calcium channel. Nature. 1986;323(6083):66–68. doi: 10.1038/323066a0
   PubMed Web of Science ®Google Scholar
• Takahashi M, Seagar MJ, Jones JF, et al. Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. Proc Natl Acad Sci, USA. 1987;84(15):5478–5482. doi: 10.1073/pnas.84.15.5478
   PubMed Web of Science ®Google Scholar
• Catterall WA. Structure and function of voltage-gated sodium and calcium channels. Curr Opin Neurobiol. 1991 Jun;1(1):5–13. doi: 10.1016/0959-4388(91)90004-Q
   PubMedGoogle Scholar
• Sharp AH, Imagawa T, Leung AT, et al. Identification and characterization of the dihydropyridine-binding subunit of the skeletal muscle dihydropyridine receptor. J Biol Chem. 1987;262(25):12309–12315. doi: 10.1016/S0021-9258(18)45353-7
   PubMed Web of Science ®Google Scholar
• Striessnig J, Knaus HG, Grabner M, et al. Photoaffinity labelling of the phenylalkylamine receptor of the skeletal muscle transverse-tubule calcium channel. FEBS Lett. 1987;212(2):247–253. doi: 10.1016/0014-5793(87)81354-6
   PubMed Web of Science ®Google Scholar
• Leung AT, Imagawa T, Campbell KP. Structural characterization of the 1,4-dihydropyridine receptor of the voltage-dependent Ca2+ channel from rabbit skeletal muscle. Evidence for two distinct high molecular weight subunits. J Biol Chem. 1987;262(17):7943–7946. doi: 10.1016/S0021-9258(18)47507-2
   PubMed Web of Science ®Google Scholar
• Jay SD, Ellis SB, McCue AF, et al. Primary structure of the gamma subunit of the DHP-sensitive calcium channel from skeletal muscle. Science. 1990;248:490–492. doi: 10.1126/science.2158672
   PubMed Web of Science ®Google Scholar
• Ruth P, Röhrkasten A, Biel M, et al. Primary structure of the beta subunit of the DHP-sensitive calcium channel from skeletal muscle. Science. 1989;245:1115–1118. doi: 10.1126/science.2549640
   PubMed Web of Science ®Google Scholar
• Vaghy PL, Striessnig J, Miwa K, et al. Identification of a novel 1,4-dihydropyridine- and phenylalkylamine-binding polypeptide in calcium channel preparations. J Biol Chem. 1987;262(29):14337–14342. doi: 10.1016/S0021-9258(18)47943-4
   PubMed Web of Science ®Google Scholar
• Nunoki K, Florio V, Catterall WA. Activation of purified calcium channels by stoichiometric protein phosphorylation. Proc Natl Acad Sci, USA. 1989;86(17):6816–6820. doi: 10.1073/pnas.86.17.6816
   PubMed Web of Science ®Google Scholar
• Tanabe T, Takeshima H, Mikami A, et al. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature. 1987;328(6128):313–318. doi: 10.1038/328313a0
   PubMed Web of Science ®Google Scholar
• Ellis SB, Williams ME, Ways NR, et al. Sequence and expression of mRNAs encoding the α1 and α2 subunits of a DHP-sensitive calcium channel. Science. 1988;241(4873):1661–1664. doi: 10.1126/science.2458626
   PubMed Web of Science ®Google Scholar
• De Jongh KS, Warner C, Catterall WA. Subunits of purified calcium channels. α2 and δ are encoded by the same gene. J Biol Chem. 1990;265:14738–14741. doi: 10.1016/S0021-9258(18)77174-3
   PubMed Web of Science ®Google Scholar
• Jay SD, Sharp AH, Kahl SD, et al. Structural characterization of the dihydropyridine-sensitive calcium channel alpha-2 subunit and the associated delta peptides. J Biol Chem. 1991;266:3287–3293. doi: 10.1016/S0021-9258(18)49986-3
   PubMed Web of Science ®Google Scholar
• Davies A, Kadurin I, Alvarez-Laviada A, et al. The α2δ subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function. Proc Natl Acad Sci, USA. 2010;107(4):1255–1690. doi: 10.1073/pnas.0908735107
   Web of Science ®Google Scholar
• Hoppa MB, Lana B, Margas W, et al. α 2 δ expression sets presynaptic calcium channel abundance and release probability. Nature. 2012;486(7401):122–125. doi: 10.1038/nature11033
   PubMed Web of Science ®Google Scholar
• Armstrong CM, Bezanilla F. Currents related to movement of the gating particles of the sodium channels. Nature. 1973;242(5398):459–461. doi: 10.1038/242459a0
   PubMed Web of Science ®Google Scholar
• Armstrong CM, Benzanilla F. Charge movement associated with the opening and closing of the activation gates of the Na channels. J Gen Physiol. 1974;63:533–552. doi: 10.1085/jgp.63.5.533
   PubMed Web of Science ®Google Scholar
• Kuzmenkin A, Bezanilla F, Correa AM. Gating of the bacterial sodium channel, NaChBac: voltage-dependent charge movement and gating currents. J Gen Physiol. 2004;124(4):349–356. doi: 10.1085/jgp.200409139
   PubMed Web of Science ®Google Scholar
• Hirschberg B, Rovner A, Lieberman M, et al. Transfer of twelve charges is needed to open skeletal muscle Na+ channels. J Gen Physiol. 1995;106(6):1053–1068. doi: 10.1085/jgp.106.6.1053
   PubMed Web of Science ®Google Scholar
• Catterall WA. Ion channel voltage sensors: structure, function, and pathophysiology. Neuron. 2010;67(6):915–928. doi: 10.1016/j.neuron.2010.08.021
   PubMed Web of Science ®Google Scholar
• Catterall WA. Voltage-dependent gating of sodium channels: correlating structure and function. Trends Neurosci. 1986;9:7–10. doi: 10.1016/0166-2236(86)90004-4
   Web of Science ®Google Scholar
• Catterall WA. Molecular properties of voltage-sensitive sodium channels. Annu Rev Biochem. 1986;55(1):953–985. doi: 10.1146/annurev.bi.55.070186.004513
   PubMedGoogle Scholar
• Stuhmer W, Conti F, Suzuki H, et al. Structural parts involved in activation and inactivation of the sodium channel. Nature. 1989;339(6226):597–603. doi: 10.1038/339597a0
   PubMed Web of Science ®Google Scholar
• Papazian DM, Timpe LC, Jan YN, et al. Alteration of voltage-dependence of Shaker potassium channel by mutations in the S4 sequence. Nature. 1991;349(6307):305–310. doi: 10.1038/349305a0
   PubMed Web of Science ®Google Scholar
• Kontis KJ, Rounaghi A, Goldin AL. Sodium channel activation gating is affected by substitutions of voltage sensor positive charges in all four domains. J Gen Physiol. 1997;110(4):391–401. doi: 10.1085/jgp.110.4.391
   PubMed Web of Science ®Google Scholar
• Aggarwal SK, MacKinnon R. Contribution of the S4 segment to gating charge in the Shaker potassium channel. Neuron. 1996;16:1169–1177. doi: 10.1016/S0896-6273(00)80143-9
   PubMed Web of Science ®Google Scholar
• Rogers JC, Qu Y, Tanada TN, et al. 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. J Biol Chem. 1996;271:15950–15962. doi: 10.1074/jbc.271.27.15950
   PubMed Web of Science ®Google Scholar
• Cestèle 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;21:919–931. doi: 10.1016/S0896-6273(00)80606-6
   PubMed Web of Science ®Google Scholar
• Yang N, George AL, Horn R. Molecular basis of charge movement in voltage-gated sodium channels. Neuron. 1996;16(1):113–122. doi: 10.1016/S0896-6273(00)80028-8
   PubMed Web of Science ®Google Scholar
• Yang N, George AL, Horn R. Probing the outer vestibule of a sodium channel voltage sensor. Biophys J. 1997;73(5):2260–2268. doi: 10.1016/S0006-3495(97)78258-4
   PubMed Web of Science ®Google Scholar
• DeCaen PG, Yarov-Yarovoy V, Zhao Y, et al. Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation. Proc Natl Acad Sci, USA. 2008;105(39):15142–15147. doi: 10.1073/pnas.0806486105
   PubMed Web of Science ®Google Scholar
• Vargas E, Yarov-Yarovoy V, Khalili-Araghi F, et al. An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations. J Gen Physiol. 2012;140(6):587–594. doi: 10.1085/jgp.201210873
   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;62(4):375–391. doi: 10.1085/jgp.62.4.375
   PubMed Web of Science ®Google Scholar
• Vassilev PM, Scheuer T, Catterall WA. Identification of an intracellular peptide segment involved in sodium channel inactivation. Science. 1988;241(4873):1658–1661. doi: 10.1126/science.2458625
   PubMed Web of Science ®Google Scholar
• Vassilev P, Scheuer T, Catterall WA. Inhibition of inactivation of single sodium channels by a site-directed antibody. Proc Natl Acad Sci, USA. 1989;86(20):8147–8151. doi: 10.1073/pnas.86.20.8147
   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, USA. 1992;89:10910–10914. doi: 10.1073/pnas.89.22.10910
   PubMed Web of Science ®Google Scholar
• Eaholtz G, Scheuer T, Catterall WA. Restoration of inactivation and block of open sodium channels by an inactivation gate peptide. Neuron. 1994;12(5):1041–1048. doi: 10.1016/0896-6273(94)90312-3
   PubMed Web of Science ®Google Scholar
• Eaholtz G, Zagotta WN, Catterall WA. Kinetic analysis of block of open sodium channels by a peptide containing the isoleucine, phenylalanine, and methionine (IFM) motif from the inactivation gate. J Gen Physiol. 1998;111(1):75–82. doi: 10.1085/jgp.111.1.75
   PubMed Web of Science ®Google Scholar
• Rohl CA, Boeckman FA, Baker C, et al. Solution structure of the sodium channel inactivation gate. Biochemistry. 1999;38(3):855–861. doi: 10.1021/bi9823380
   PubMed Web of Science ®Google Scholar
• Adelman WJ, Palti Y. The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid Loligo pealei. J Gen Physiol. 1968;54:589–606. doi: 10.1085/jgp.54.5.589
   Web of Science ®Google Scholar
• Vilin YY, Ruben PC. Slow inactivation in voltage-gated sodium channels: molecular substrates and contributions to channelopathies. Cell Biochem Biophys. 2001;35(2):171–90. doi: 10.1385/CBB:35:2:171. PMID: 11892790.
   PubMed Web of Science ®Google Scholar
• Rudy B. Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance. Journal of Physiology. 1978;283(1):1–21. doi: 10.1113/jphysiol.1978.sp012485
   PubMedGoogle Scholar
• Balser JR, Nuss HB, Chiamvimonvat N, et al. External pore residue mediates slow inactivation in μ1 rat skeletal muscle sodium channels. J Physiol (Lond). 1996;494:431–442. doi: 10.1113/jphysiol.1996.sp021503
   Google Scholar
• Balser JR, Nuss HB, Chiamvimonvat N, et al. External pore residue mediates slow inactivation in μ1 rat skeletal muscle sodium channels. J Physiol. 1996;494(Pt 2):431–442. doi: 10.1113/jphysiol.1996.sp021503
   PubMed Web of Science ®Google Scholar
• Xiong W, Farukhi YZ, Tian Y, et al. A conserved ring of charge in mammalian Na+ channels: a molecular regulator of the outer pore conformation during slow inactivation. J Physiol. 2006;576(Pt 3):739–754. doi: 10.1113/jphysiol.2006.115105
   PubMed Web of Science ®Google Scholar
• Noda M, Suzuki H, Numa S, et al. A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II. FEBS Lett. 1989;259(1):213–216. doi: 10.1016/0014-5793(89)81531-5
   PubMed Web of Science ®Google Scholar
• Heinemann SH, Terlau H, Stühmer W, et al. Calcium channel characteristics conferred on the sodium channel by single mutations. Nature. 1992;356(6368):441–443. doi: 10.1038/356441a0
   PubMed Web of Science ®Google Scholar
• Schlief T, Schönherr R, Imoto K, et al. Pore properties of rat brain II sodium channels mutated in the selectivity filter domain. Eur Biophys J. 1996;25(2):75–91. doi: 10.1007/s002490050020
   PubMed Web of Science ®Google Scholar
• Ren D, Navarro B, Xu H, et al. A prokaryotic voltage-gated sodium channel. Science. 2001;294(5550):2372–2375. doi: 10.1126/science.1065635
   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;475(7356):353–358. doi: 10.1038/nature10238
   PubMed Web of Science ®Google Scholar
• Wisedchaisri G, Tonggu L, McCord E, et al. Resting-state structure and gating mechanism of a voltage-gated sodium channel. Cell. 2019;178(4):993–1003.e12. doi: 10.1016/j.cell.2019.06.031
   PubMed Web of Science ®Google Scholar
• Chakrabarti N, Ing C, Payandeh J, et al. Catalysis of Na+ permeation in the bacterial sodium channel NaVAb. Proc Natl Acad Sci, USA. 2013;110(28):11331–11336. doi: 10.1073/pnas.1309452110
   PubMed Web of Science ®Google Scholar
• Pavlov E, Bladen C, Winkfein R, et al. The pore, not cytoplasmic domains, underlies inactivation in a prokaryotic sodium channel. Biophys J. 2005;89(1):232–242. doi: 10.1529/biophysj.104.056994
   PubMed Web of Science ®Google Scholar
• El-Din TM G, Lenaeus MJ, Ramanadane K, et al. Molecular dissection of multiphase inactivation of the bacterial sodium channel NaVAb. J Gen Physiol. 2019;151(2):174–185. doi: 10.1085/jgp.201711884
   PubMed Web of Science ®Google Scholar
• Payandeh J, Gamal El-Din TM, Scheuer T, et al. Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. Nature. 2012;486(7401):135–139. doi: 10.1038/nature11077
   PubMed Web of Science ®Google Scholar
• Ong BH, Tomaselli GF, Balser JR. A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence. J Gen Physiol. 2000;116(5):653–662. doi: 10.1085/jgp.116.5.653
   PubMed Web of Science ®Google Scholar
• Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977;69(4):497–515. doi: 10.1085/jgp.69.4.497
   PubMed Web of Science ®Google Scholar
• Hondeghem LM, Katzung BG. Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium channel blocking drugs. Annu Rev Pharmacol Toxicol. 1984;24:387–423. doi: 10.1146/annurev.pa.24.040184.002131
   PubMed Web of Science ®Google Scholar
• El-Din TM G, Lenaeus MJ, Zheng N, et al. Fenestrations control resting-state block of a voltage-gated sodium channel. Proc Natl Acad Sci, USA. 2018;115:13111–13116. doi: 10.1073/pnas.1814928115
   PubMed Web of Science ®Google Scholar
• Koishi R, Xu H, Ren D, et al. A superfamily of voltage-gated sodium channels in bacteria. J Biol Chem. 2004;279(10):9532–9538. doi: 10.1074/jbc.M313100200
   PubMed Web of Science ®Google Scholar
• Payandeh J, Minor DL Jr. Bacterial voltage-gated sodium channels (BacNavs) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart. J Mol Biol. 2015;427(1):3–30. doi: 10.1016/j.jmb.2014.08.010
   PubMed Web of Science ®Google Scholar
• Almers W, McCleskey EW, Palade PT. A nonselective cation conductance in frog muscle membrane blocked by micromolar external Ca++. J Physiol. 1984;353:565–583. doi: 10.1113/jphysiol.1984.sp015351
   PubMed Web of Science ®Google Scholar
• Almers W, McCleskey EW. The nonselective conductance due to calcium channels in frog muscle: calcium-selectivity in a single file pore. J Physiol. 1984;353:585–608. doi: 10.1113/jphysiol.1984.sp015352
   PubMed Web of Science ®Google Scholar
• Hess P, Tsien RW. Mechanism of ion permeation through calcium channels. Nature. 1984;309(5967):453–456. doi: 10.1038/309453a0
   PubMed Web of Science ®Google Scholar
• Sather WA, McCleskey EW. Permeation and selectivity in calcium channels. Annu Rev Physiol. 2003;65(1):133–159. doi: 10.1146/annurev.physiol.65.092101.142345
   PubMedGoogle Scholar
• Tang L, Gamal El-Din TM, Payandeh J, et al. Structural basis for Ca2+ selectivity of a voltage-gated calcium channel. Nature. 2014;505(7481):56–61. doi: 10.1038/nature12775
   PubMed Web of Science ®Google Scholar
• Glossmann H, Striessnig J. Calcium channels. Vitam Horm. 1988;44:155–328.
   PubMed Web of Science ®Google Scholar
• Godfraind T. Discovery and development of calcium channel blockers. Front Pharmacol. 2017;8:286. doi: 10.3389/fphar.2017.00286
   PubMed Web of Science ®Google Scholar
• Sampson KJ, Kass RK. Antiarrhythmic drugs. Goodman & Gilman’s pharmacological basis of therapeutics. 12th ed. McGraw Hill, New York. 2011. pp. 815–848.
   Google Scholar
• Striessnig J. Pharmacology, structure and function of cardiac L-type calcium channels. Cell Physiol Biochem. 1999;9(4–5):242–269. doi: 10.1159/000016320
   PubMedGoogle Scholar
• Hofmann F, Lacinová L, Klugbauer N. Voltage-dependent calcium channels: from structure to function. Rev Physiol Biochem Pharmacol. 1999;139:33–87.
   PubMed Web of Science ®Google Scholar
• Hockerman GH, Peterson BZ, Johnson BD, et al. Molecular determinants of drug binding and action on L-type calcium channels. Annu Rev Pharmacol Toxicol. 1997;37(1):361–396. doi: 10.1146/annurev.pharmtox.37.1.361
   PubMedGoogle Scholar
• Bean BP, Cohen CJ, Tsien RW. Lidocaine block of cardiac sodium channels. J Gen Physiol. 1983;81(5):613–642. doi: 10.1085/jgp.81.5.613
   PubMed Web of Science ®Google Scholar
• Hondeghem LM, Katzung BG. Timed- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels. Biochim Biophys Acta. 1977;472:373–398. doi: 10.1016/0304-4157(77)90003-X
   PubMed Web of Science ®Google Scholar
• Bean BP. Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci, USA. 1984;81(20):6388–6392. doi: 10.1073/pnas.81.20.6388
   PubMed Web of Science ®Google Scholar
• Striessnig J, Glossmann H, Catterall WA. Identification of a phenylalkylamine binding region within the α1 subunit of skeletal muscle Ca channels. Proc Natl Acad Sci, USA. 1990;87:9108–9112. doi: 10.1073/pnas.87.23.9108
   PubMed Web of Science ®Google Scholar
• Kraus R, Reichl B, Kimball SD, et al. Identification of benz(othi)azepine-binding regions within L-type calcium channel α1 subunits. J Biol Chem. 1996;271(33):20113–20118. doi: 10.1074/jbc.271.33.20113
   PubMed Web of Science ®Google Scholar
• Striessnig J, Murphy BJ, Catterall WA. The dihydropyridine receptor of L-type Ca2+ channels: identification of binding domains for (+)-[3H]PN200-110 and [3H]azidopine within the alpha-1 subunit. Proc Natl Acad Sci, USA. 1991;88:10769–10773. doi: 10.1073/pnas.88.23.10769
   PubMed Web of Science ®Google Scholar
• Nakayama H, Taki M, Striessnig J, et al. Identification of 1,4-dihydropyridine binding regions within the α1 subunit of skeletal muscle Ca channels by photoaffinity labeling with diazipine. Proc Natl Acad Sci, USA. 1991;88:9203–9207. doi: 10.1073/pnas.88.20.9203
   PubMed Web of Science ®Google Scholar
• Hockerman GH, Johnson BD, Scheuer T, et al. Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels. J Biol Chem. 1995;270:22119–22122. doi: 10.1074/jbc.270.38.22119
   PubMed Web of Science ®Google Scholar
• Hockerman GH, Johnson BD, Abbott MR, et al. Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels in transmembrane segment IIIS6 and the pore region of the a1 subunit. J Biol Chem. 1997;272:18759–18765. doi: 10.1074/jbc.272.30.18759
   PubMed Web of Science ®Google Scholar
• Peterson BZ, Hockerman GH, Abbot MR, et al. Analysis of the dihydropyridine receptor site of L-type calcium channels by alanine-scanning mutagenesis. J Biol Chem. 1997;272:18752–18758. doi: 10.1074/jbc.272.30.18752
   PubMed Web of Science ®Google Scholar
• Hockerman GH, Dilmac N, Scheuer T. Molecular determinants of diltiazem block in domains III S6 and IVS6 of L-type Ca channels. Mol Pharmacol. 2000;58:1264–1270. doi: 10.1124/mol.58.6.1264
   PubMed Web of Science ®Google Scholar
• Mitterdorfer J, Wang ZY, Sinnegger MJ, et al. Two amino acid residues in the IIIS5 segment of L-type calcium channels differentially contribute to 1,4-dihydropyridine sensitivity. J Biol Chem. 1996;271(48):30330–30335. doi: 10.1074/jbc.271.48.30330
   PubMed Web of Science ®Google Scholar
• Schuster A, Lacinová L, Klugbauer N, et al. The IVS6 segment of the L-type calcium channel is critical for the action of dihydropyridines and phenylalkylamines. EMBO J. 1996;15(10):2365–2370. doi: 10.1002/j.1460-2075.1996.tb00592.x
   PubMed Web of Science ®Google Scholar
• Ito H, Klugbauer N, Hofmann F. Transfer of the high affinity dihydropyridine sensitivity from L-type to non-L-type calcium channel. Mol Pharmacol. 1997;52(4):735–740. doi: 10.1124/mol.52.4.735
   PubMed Web of Science ®Google Scholar
• Qian H, Patriarchi T, Price JL, et al. Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the beta2-adrenergic receptor in neurons. Sci Signal. 2017 Jan 24;10(463). doi: 10.1126/scisignal.aaf9659
   Web of Science ®Google Scholar
• Hockerman GH, Peterson BZ, Sharp E, et al. Construction of a high-affinity receptor site for dihydropyridine agonists and antagonists by single amino acid substitutions in a non-L-type Ca2+ channel. Proc Natl Acad Sci, USA. 1997;94(26):14906–14911. doi: 10.1073/pnas.94.26.14906
   PubMed Web of Science ®Google Scholar
• Sinnegger MJ, Wang ZY, Grabner M, et al. Nine L-type amino acid residues confer full 1,4-dihydropyridine sensitivity to the neuronal calcium channel α1A subunit. J Biol Chem. 1997;272(44):27686–27693. doi: 10.1074/jbc.272.44.27686
   PubMed Web of Science ®Google Scholar
• Tang L, Gamal El-Din TM, Swanson TM, et al. Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs. Nature. 2016;537(7618):117–121. doi: 10.1038/nature19102
   PubMed Web of Science ®Google Scholar
• Tang L, Gamal El-Din TM, Lenaeus MJ, et al. Structural basis for diltiazem block of a voltage-gated Ca2+ channel. Mol Pharmacol. 2019;96(4):485–492. doi: 10.1124/mol.119.117531
   PubMed Web of Science ®Google Scholar
• Wu J, Yan Z, Li Z, et al. Structure of the voltage-gated calcium channel CaV.1 at 3.6 a resolution. Nature. 2016;537(7619):191–196. doi: 10.1038/nature19321
   PubMed Web of Science ®Google Scholar
• Zhao Y, Huang G, Wu J, et al. Molecular basis for ligand modulation of a mammalian voltage-gated calcium channel. Cell. 2019;177(6):1495–1506.e12. doi: 10.1016/j.cell.2019.04.043
   PubMed 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. Science. 2018;362(6412). doi: 10.1126/science.aau2486
   Web of Science ®Google Scholar
• Shen H, Liu D, Wu K, et al. Structures of human NaV.7 channel in complex with auxiliary subunits and animal toxins. Science. 2019;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 Nav.2 by the μ-conotoxin KIIIA. Science. 2019;363(6433):1309–1313. doi: 10.1126/science.aaw2999
   PubMed Web of Science ®Google Scholar
• Fan X, Huang J, Jin X, et al. Cryo-EM structure of human voltage-gated sodium channel Nav.6. Proc Natl Acad Sci U S A. 2023;120(5):e2220578120. doi: 10.1073/pnas.2220578120
   PubMed Web of Science ®Google Scholar
• Zhang J, Shi Y, Huang Z, et al. Structural basis for NaV.7 inhibition by pore blockers Nat Struct Mol Biol. Nat Struct Mol Biol. 2022;29(12):1208–1216. doi: 10.1038/s41594-022-00860-1
   PubMed Web of Science ®Google Scholar
• Li Y, Yuan T, Huang B, et al. Structure of human NaV.6 channel reveals Na+ selectivity and pore blockade by 4,9-anhydro-tetrodotoxin. Nat Commun. 2023;14(1):1030. doi: 10.1038/s41467-023-36766-9
   PubMed Web of Science ®Google Scholar
• Jiang D, Shi H, Tonggu L, et al. Structure of the cardiac sodium channel. Cell. 2020;180(1):122–134.e10. doi: 10.1016/j.cell.2019.11.041
   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 Nav1.5. Angew Chem Int Ed Engl. 2021;60(20):11474–11480. doi: 10.1002/anie.202102196
   PubMed Web of Science ®Google Scholar
• Zhao Y, Huang G, Wu Q, et al. Cryo-EM structures of apo and antagonist-bound human CaV.1. Nature. 2019;576(7787):492–497. doi: 10.1038/s41586-019-1801-3
   PubMed Web of Science ®Google Scholar
• Gao S, Yao X, Yan N. Structure of human Cav2.2 channel blocked by the painkiller ziconotide. Nature. 2021;596(7870):143–147. doi: 10.1038/s41586-021-03699-6
   PubMed Web of Science ®Google 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;184(20):5151–5162.e11. doi: 10.1016/j.cell.2021.08.021
   PubMed Web of Science ®Google Scholar
• Jiang D, Gamal El-Din T, Zheng N, et al. Expression and purification of the cardiac sodium channel Nav1.5. Methods Enzymol. 2021;653:89–101.
   PubMed Web of Science ®Google Scholar
• Sokolov S, Scheuer T, Catterall WA. Ion permeation through a voltage-sensitive gating pore in brain sodium channels having voltage sensor mutations. Neuron. 2005;47(2):183–189. doi: 10.1016/j.neuron.2005.06.012
   PubMed Web of Science ®Google Scholar
• Sokolov S, Scheuer T, Catterall WA. Gating pore current in an inherited ion channelopathy. Nature. 2007;446(7131):76–78. doi: 10.1038/nature05598
   PubMed Web of Science ®Google Scholar
• Struyk AF, Cannon SC. A Na+ channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore. J Gen Physiol. 2007;130(1):11–20. doi: 10.1085/jgp.200709755
   PubMed Web of Science ®Google Scholar
• Sokolov S, Scheuer T, Catterall WA. Depolarization-activated gating pore current conducted by mutant sodium channels in potassium-sensitive normokalemic periodic paralysis. Proc Natl Acad Sci U S A. 2008;105(50):19980–19985. doi: 10.1073/pnas.0810562105
   PubMed Web of Science ®Google Scholar
• Moreau A, Gosselin-Badaroudine P, Boutjdir M, et al. Mutations in the voltage sensors of domains I and II of Nav1.5 that are associated with arrhythmias and dilated cardiomyopathy generate gating pore currents. Front Pharmacol. 2015;6:301. doi: 10.3389/fphar.2015.00301
   PubMed Web of Science ®Google Scholar
• El-Din TM G, Lantin T, Tschumi CW, et al. Autism-associated mutations in Kv7/KCNQ channels induce gating pore current. Proc Natl Acad Sci, USA. 2021;118(45). doi: 10.1073/pnas.2112666118
   Web of Science ®Google Scholar
• Jiang D, Gamal El-Din TM, Ing C, et al. Structural basis for gating pore current in periodic paralysis. Nature. 2018;557(7706):590–594. doi: 10.1038/s41586-018-0120-4
   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;71(6):3110–3125. doi: 10.1016/S0006-3495(96)79505-X
   PubMed Web of Science ®Google Scholar
• Benndorf K. Properties of single cardiac Na channels at 35 degrees C. J Gen Physiol. 1994;104(5):801–820. doi: 10.1085/jgp.104.5.801
   PubMed Web of Science ®Google Scholar
• Ramos E, O’Leary ME. State-dependent trapping of flecainide in the cardiac sodium channel. J Physiol. 2004;560(Pt 1):37–49. doi: 10.1113/jphysiol.2004.065003
   PubMed Web of Science ®Google Scholar
• Lenaeus ML, Gamal El-Din TM, Tonggu L, et al. Structural basis for inhibition of the cardiac sodium channels by the atypical antiarrhythmic drug ranolazine. Nat Cardiovasc Res. 2023;2(6):587–594. doi: 10.1038/s44161-023-00271-5
   Google Scholar
• Catterall WA, Cestele S, Yarov-Yarovoy V, et al. Voltage-gated ion channels and gating modifier toxins. Toxicon. 2007;49(2):124–141. doi: 10.1016/j.toxicon.2006.09.022
   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, USA. 2011;108(37):15426–15431. doi: 10.1073/pnas.1112320108
   PubMed Web of Science ®Google Scholar
• Leipold E, Lu S, Gordon D, et al. Combinatorial interaction of scorpion toxins lqh-2, lqh-3, and LqhalphaIT with sodium channel receptor sites-3. Mol Pharmacol. 2004;65(3):685–691. doi: 10.1124/mol.65.3.685
   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;117(6):505–518. doi: 10.1085/jgp.117.6.505
   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;12(1):128. doi: 10.1038/s41467-020-20078-3
   PubMed Web of Science ®Google Scholar
• Sather WA, Yang J, Tsien RW. Structural basis of ion channel permeation and selectivity. Curr Opin Neurobiol. 1994;4:313–323. doi: 10.1016/0959-4388(94)90091-4
   PubMedGoogle Scholar
• Ragsdale DS, McPhee JC, Scheuer T, et al. Molecular determinants of state-dependent block of sodium channels by local anesthetics. Science. 1994;265:1724–1728. doi: 10.1126/science.8085162
   PubMed 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;170(3):470–482 e11. doi: 10.1016/j.cell.2017.06.039
   PubMed Web of Science ®Google Scholar