Skip to main content
SpringerLink
Log in

Forty Years of Sodium Channels: Structure, Function, Pharmacology, and Epilepsy

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Voltage-gated sodium channels initiate action potentials in brain neurons. In the 1970s, much was known about the function of sodium channels from measurements of ionic currents using the voltage clamp method, but there was no information about the sodium channel molecules themselves. As a postdoctoral fellow and staff scientist at the National Institutes of Health, I developed neurotoxins as molecular probes of sodium channels in cultured neuroblastoma cells. During those years, Bruce Ransom and I crossed paths as members of the laboratories of Marshall Nirenberg and Philip Nelson and shared insights about sodium channels in neuroblastoma cells from my work and electrical excitability and synaptic transmission in cultured spinal cord neurons from Bruce’s pioneering electrophysiological studies. When I established my laboratory at the University of Washington in 1977, my colleagues and I used those neurotoxins to identify the protein subunits of sodium channels, purify them, and reconstitute their ion conductance activity in pure form. Subsequent studies identified the molecular basis for the main functions of sodium channels—voltage-dependent activation, rapid and selective ion conductance, and fast inactivation. Bruce Ransom and I re-connected in the 1990s, as ski buddies at the Winter Conference on Brain Research and as faculty colleagues at the University of Washington when Bruce became our founding Chair of Neurology and provided visionary leadership of that department. In the past decade my work on sodium channels has evolved into structural biology. Molecular modeling and X-ray crystallographic studies have given new views of sodium channel function at atomic resolution. Sodium channels are also the molecular targets for genetic diseases, including Dravet Syndrome, an intractable pediatric epilepsy disorder with major co-morbidities of cognitive deficit, autistic-like behaviors, and premature death that is caused by loss-of-function mutations in the brain sodium channel NaV1.1. Our work on a mouse genetic model of this disease has shown that its multi-faceted pathophysiology and co-morbidities derive from selective loss of electrical excitability and action potential firing in GABAergic inhibitory neurons, which disinhibits neural circuits throughout the brain and leads directly to the epilepsy, premature death and complex co-morbidities of this disease. It has been rewarding for me to use our developing knowledge of sodium channels to help understand the pathophysiology and to suggest potential therapeutic approaches for this devastating childhood disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Reprinted from [79]

Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ransom BR, Barker JL, Nelson PG (1975) Two mechanisms for poststimulus hyperpolarisations in cultured mammalian neurones. Nature 256:424–425

    Article  CAS  PubMed  Google Scholar 

  2. Ransom BR, Bullock PN, Nelson PG (1977) Mouse spinal cord in cell culture. III: neuronal chemosensitivity and its relationship to synaptic activity. J Neurophysiol 40:1163–1177

    CAS  PubMed  Google Scholar 

  3. Ransom BR, Christian CN, Bullock PN, Nelson PG (1977) Mouse spinal cord in cell culture. II: synaptic activity and circuit behavior. J Neurophysiol 40:1151–1162

    CAS  PubMed  Google Scholar 

  4. Nelson PG, Ransom BR, Henkart M, Bullock PN (1977) Mouse spinal cord in cell culture. IV: modulation of inhibitory synaptic function. J Neurophysiol 40:1178–1187

    CAS  PubMed  Google Scholar 

  5. Ransom BR, Neale E, Henkart M, Bullock PN, Nelson PG (1977) Mouse spinal cord in cell culture. I: morphology and intrinsic neuronal electrophysiologic properties. J Neurophysiol 40:1132–1150

    CAS  PubMed  Google Scholar 

  6. Catterall WA, Nirenberg M (1973) Sodium uptake associated with activation of action potential ionophores of cultured neuroblastoma and muscle cells. Proc Natl Acad Sci USA 70:3759–3763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Black JA, Yokoyama S, Waxman SG, Oh Y, Zur KB, Sontheimer H, Higashida H, Ransom BR (1994) Sodium channel mRNAs in cultured spinal cord astrocytes: in situ hybridization in identified cell types. Brain Res Mol Brain Res 23:235–245

    Article  CAS  PubMed  Google Scholar 

  8. Black JA, Westenbroek R, Minturn JE, Ransom BR, Catterall WA, Waxman SG (1995) Isoform-specific expression of sodium channels in astrocytes in vitro: immunocytochemical observations. Glia 14:133–144. doi:10.1002/glia.440140208

    Article  CAS  PubMed  Google Scholar 

  9. Brown AM, Westenbroek RE, Catterall WA, Ransom BR (2001) Axonal L-type Ca2+ channels and anoxic injury in rat CNS white matter. J Neurophysiol 85:900–911

    CAS  PubMed  Google Scholar 

  10. Chen C, Bharucha V, Chen Y, Westenbroek RE, Brown A, Malhotra JD, Jones D, Avery C, Gillespie PJ, 3rd, Kazen-Gillespie KA, Kazarinova-Noyes K, Shrager P, Saunders TL, Macdonald RL, Ransom BR, Scheuer T, Catterall WA, Isom LL (2002) Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel β2-subunits. Proc Natl Acad Sci USA. 99:17072–17077. doi:10.1073/pnas.212638099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hille B (2001) Ionic channels of excitable membranes, 3rd edn. Sinauer Associates Inc., Sunderland, MA

    Google Scholar 

  12. Lehman-Horn F, Jurkat-Rott K (1999) Voltage-gated ion channels and hereditary disease. Physiol Rev 79:1317–1372

    Google Scholar 

  13. Catterall WA, Dib-Hajj S, Meisler MH, Pietrobon D (2008) Inherited neuronal ion channelopathies: new windows on complex neurological diseases. J Neurosci 28:11768–11777. doi:10.1523/JNEUROSCI.3901-08.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Catterall WA (1980) Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Annu Rev Pharmacol Toxicol 20:15–43

    Article  CAS  PubMed  Google Scholar 

  16. Beneski DA, Catterall WA (1980) Covalent labeling of protein components of the sodium channel with a photoactivable derivative of scorpion toxin. Proc Natl Acad Sci USA 77:639–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hartshorne RP, Catterall WA (1981) Purification of the saxitoxin receptor of the sodium channel from rat brain. Proc Natl Acad Sci USA 78:4620–4624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hartshorne RP, Messner DJ, Coppersmith JC, Catterall WA (1982) The saxitoxin receptor of the sodium channel from rat brain. Evidence for two nonidentical β subunits. J Biol Chem 257:13888–13891

    CAS  PubMed  Google Scholar 

  19. Hartshorne RP, Catterall WA (1984) The sodium channel from rat brain: purification and subunit composition. J Biol Chem 259:1667–1675

    CAS  PubMed  Google Scholar 

  20. Talvenheimo JA, Tamkun MM, Catterall WA (1982) Reconstitution of neurotoxin-stimulated sodium transport by the voltage-sensitive sodium channel purified from rat brain. J Biol Chem 257:11868–11871

    CAS  PubMed  Google Scholar 

  21. Tamkun MM, Talvenheimo JA, Catterall WA (1984) The sodium channel from rat brain: reconstitution of neurotoxin-activated ion flux and scorpion toxin binding from purified components. J Biol Chem 259:1676–1688

    CAS  PubMed  Google Scholar 

  22. Hartshorne RP, Keller BU, Talvenheimo JA, Catterall WA, Montal M (1985) Functional reconstitution of the purified brain sodium channel in planar lipid bilayers. Proc Natl Acad Sci USA 82:240–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Noda M, Shimizu S, Tanabe T, Takai T, Kayano T, Ikeda T, Takahashi H, Nakayama H, Kanaoka Y, Minamino N et al (1984) Primary structure of electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312:121–127

    Article  CAS  PubMed  Google Scholar 

  24. Noda M, Ikeda T, Suzuki H, Takeshima H, Takahashi T, Kuno M, Numa S (1986) Expression of functional sodium channels from cloned cDNA. Nature. 322:826–828. doi:10.1038/322826a0

    Article  CAS  PubMed  Google Scholar 

  25. Goldin AL, Snutch T, Lubbert H, Dowsett A, Marshall J, Auld V, Downey W, Fritz LC, Lester HA, Dunn R, Catterall WA, Davidson N (1986) Messenger RNA coding for only the alpha subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes. Proc Natl Acad Sci USA 83:7503–7507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Isom LL, De Jongh KS, Patton DE, Reber BFX, Offord J, Charbonneau H, Walsh K, Goldin AL, Catterall WA (1992) Primary structure and functional expression of the β1 subunit of the rat brain sodium channel. Science 256:839–842

    Article  CAS  PubMed  Google Scholar 

  27. Isom LL, Ragsdale DS, De Jongh KS, Westenbroek RE, Reber BF, Scheuer T, Catterall WA (1995) Structure and function of the β2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell 83:433–442

    Article  CAS  PubMed  Google Scholar 

  28. Catterall WA (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26:13–25

    Article  CAS  PubMed  Google Scholar 

  29. Brackenbury WJ, Isom LL (2011) Na channel β subunits: overachievers of the ion channel family. Front Pharmacol 2:53. doi:10.3389/fphar.2011.00053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Armstrong CM, Bezanilla F (1973) Currents related to movement of the gating particles of the sodium channels. Nature 242:459–461

    Article  CAS  PubMed  Google Scholar 

  31. Catterall WA (1986) Voltage-dependent gating of sodium channels: correlating structure and function. Trends Neurosci 9:7–10

    Article  CAS  Google Scholar 

  32. Catterall WA (1986) Molecular properties of voltage-sensitive sodium channels. Annu Rev Biochem. 55:953–985. doi:10.1146/annurev.bi.55.070186.004513

    Article  CAS  PubMed  Google Scholar 

  33. Yarov-Yarovoy V, Baker D, Catterall WA (2006) Voltage sensor conformations in the open and closed states in ROSETTA structural models of K+ channels. Proc Natl Acad Sci USA. 103:7292–7297. doi:10.1073/pnas.0602350103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Guy HR, Seetharamulu P (1986) Molecular model of the action potential sodium channel. Proc Natl Acad Sci USA 83:508–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yarov-Yarovoy V, DeCaen PG, Westenbroek RE, Pan CY, Scheuer T, Baker D, Catterall WA (2012) Structural basis for gating charge movement in the voltage sensor of a sodium channel. Proc Natl Acad Sci USA 109:E93–E102. doi:10.1073/pnas.1118434109

    Article  CAS  PubMed  Google Scholar 

  36. Stuhmer W, Conti F, Suzuki H, Wang XD, Noda M, Yahagi N, Kubo H, Numa S (1989) Structural parts involved in activation and inactivation of the sodium channel. Nature. 339:597–603. doi:10.1038/339597a0

    Article  CAS  PubMed  Google Scholar 

  37. Rogers JC, Qu Y, Tanada TN, Scheuer T, Catterall WA (1996) 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 271:15950–15962

    Article  CAS  PubMed  Google Scholar 

  38. Cestele S, Qu Y, Rogers JC, Rochat H, Scheuer T, Catterall WA (1998) Voltage sensor-trapping: enhanced activation of sodium channels by β-scorpion toxin bound to the S3–S4 loop in domain II. Neuron 21:919–931

    Article  CAS  PubMed  Google Scholar 

  39. Yang N, Horn R (1995) Evidence for voltage-dependent S4 movement in sodium channel. Neuron 15:213–218

    Article  CAS  PubMed  Google Scholar 

  40. Yang N, George AL Jr, Horn R (1996) Molecular basis of charge movement in voltage-gated sodium channels. Neuron 16:113–122

    Article  PubMed  Google Scholar 

  41. Yang N, George AL, Jr., Horn R (1997) Probing the outer vestibule of a sodium channel voltage sensor. Biophys J. 73:2260–2268. doi:10.1016/S0006-3495(97)78258-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. DeCaen PG, Yarov-Yarovoy V, Zhao Y, Scheuer T, Catterall WA (2008) Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation. Proc Natl Acad Sci USA 105:15142–15147. doi:10.1073/pnas.0806486105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. DeCaen PG, Yarov-Yarovoy V, Sharp EM, Scheuer T, Catterall WA (2009) Sequential formation of ion pairs during activation of a sodium channel voltage sensor. Proc Natl Acad Sci USA 106:22498–22503. doi:10.1073/pnas.0912307106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. DeCaen PG, Yarov-Yarovoy V, Scheuer T, Catterall WA (2011) Gating charge interactions with the S1 segment during activation of a Na+ channel voltage sensor. Proc Natl Acad Sci USA 108:18825–18830. doi:10.1073/pnas.1116449108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Vargas E, Yarov-Yarovoy V, Khalili-Araghi F, Catterall WA, Klein ML, Tarek M, Lindahl E, Schulten K, Perozo E, Bezanilla F, Roux B (2012) An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations. J Gen Physiol 140:587–594. doi:10.1085/jgp.201210873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Noda M, Suzuki H, Numa S, Stuhmer W (1989) A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II. FEBS Lett 259:213–216. doi:10.1016/0014-5793(89)81531-5

    Article  CAS  PubMed  Google Scholar 

  47. Terlau H, Heinemann SH, Stuhmer W, Pusch M, Conti F, Imoto K, Numa S (1991) Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II. FEBS Lett 293:93–96

    Article  CAS  PubMed  Google Scholar 

  48. Heinemann SH, Terlau H, Stuhmer W, Imoto K, Numa S (1992) Calcium channel characteristics conferred on the sodium channel by single mutations. Nature. 356:441–443. doi:10.1038/356441a0

    Article  CAS  PubMed  Google Scholar 

  49. Hodgkin AL, Huxley AF (1952) The dual effect of membrane potential on sodium conductance in the giant axon of Loligo. J Physiol 116:497–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vassilev PM, Scheuer T, Catterall WA (1988) Identification of an intracellular peptide segment involved in sodium channel inactivation. Science 241:1658–1661

    Article  CAS  PubMed  Google Scholar 

  51. West JW, Patton DE, Scheuer T, Wang Y, Goldin AL, Catterall WA (1992) A cluster of hydrophobic amino acid residues required for fast Na+-channel inactivation. Proc Natl Acad Sci USA 89:10910–10914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Eaholtz G, Scheuer T, Catterall WA (1994) Restoration of inactivation and block of open sodium channels by an inactivation gate peptide. Neuron 12:1041–1048

    Article  CAS  PubMed  Google Scholar 

  53. Rohl CA, Boeckman FA, Baker C, Scheuer T, Catterall WA, Klevit RE (1999) Solution structure of the sodium channel inactivation gate. Biochemistry 38:855–861. doi:10.1021/bi9823380

    Article  CAS  PubMed  Google Scholar 

  54. Goldin AL (2001) Resurgence of sodium channel research. Annu Rev Physiol 63:871–894. doi:10.1146/annurev.physiol.63.1.871

    Article  CAS  PubMed  Google Scholar 

  55. Ren D, Navarro B, Xu H, Yue L, Shi Q, Clapham DE (2001) A prokaryotic voltage-gated sodium channel. Science. 294:2372–2375. doi:10.1126/science.1065635

    Article  CAS  PubMed  Google Scholar 

  56. Koishi R, Xu H, Ren D, Navarro B, Spiller BW, Shi Q, Clapham DE (2004) A superfamily of voltage-gated sodium channels in bacteria. J Biol Chem 279:9532–9538. doi:10.1074/jbc.M313100200

    Article  CAS  PubMed  Google Scholar 

  57. Payandeh J, Scheuer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature. 475:353–358. doi:10.1038/nature10238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Catterall WA (1987) Common modes of drug action on Na+ channels: Local anesthetics, antiarrhythmics and anticonvulsants. Trends Pharmacol Sci 8:57–65

    Article  CAS  Google Scholar 

  59. Ragsdale DS, McPhee JC, Scheuer T, Catterall WA (1994) Molecular determinants of state-dependent block of sodium channels by local anesthetics. Science 265:1724–1728

    Article  CAS  PubMed  Google Scholar 

  60. Ragsdale DS, McPhee JC, Scheuer T, Catterall WA (1996) Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels. Proc Natl Acad Sci USA 93:9270–9275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Yarov-Yarovoy V, McPhee JC, Idsvoog D, Pate C, Scheuer T, Catterall WA (2002) Role of amino acid residues in transmembrane segments IS6 and IIS6 of the sodium channel alpha subunit in voltage-dependent gating and drug block. J Biol Chem. doi:10.1074/jbc.M206126200

    PubMed  Google Scholar 

  62. Yarov-Yarovoy V, Brown J, Sharp EM, Clare JJ, Scheuer T, Catterall WA (2001) Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na+ channel α subunit. J Biol Chem 276:20–27. doi:10.1074/jbc.M006992200

    Article  CAS  PubMed  Google Scholar 

  63. Wang GK, Quan C, Wang S (1998) A common local anesthetic receptor for benzocaine and etidocaine in voltage-gated mu1 Na+ channels. Pflugers Arch 435:293–302

    Article  CAS  PubMed  Google Scholar 

  64. Hille B (1977) Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515

    Article  CAS  PubMed  Google Scholar 

  65. Shen H, Zhou Q, Pan X, Li Z, Wu J, Yan N (2017) Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution. Science. doi:10.1126/science.aal4326

    Google Scholar 

  66. Engel J Jr., International League Against E (2001) A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE task force on classification and terminology. Epilepsia 42:796–803

    Article  PubMed  Google Scholar 

  67. Dravet C, Bureau M, Guerrini R, Giraud N, Roger J (1992) Severe myoclonic epilepsy in infants. In: Roger J, Dravet C, Bureau M, Dreifus FE, Perret A, Wolf P (eds) Epileptic sndromes in infancy, childhood and adolescence, 2nd edn. John Libbey, London, pp 75–102

    Google Scholar 

  68. Yu FH, Mantegazza M, Westenbroek RE, Robbins CA, Kalume F, Burton KA, Spain WJ, McKnight GS, Scheuer T, Catterall WA (2006) Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci 9:1142–1149. doi:10.1038/nn1754

    Article  CAS  PubMed  Google Scholar 

  69. Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, Takeuchi T, Itohara S, Yanagawa Y, Obata K, Furuichi T, Hensch TK, Yamakawa K (2007) Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci 27:5903–5914. doi:10.1523/JNEUROSCI.5270-06.2007

    Article  CAS  PubMed  Google Scholar 

  70. Oakley JC, Cho AR, Cheah CS, Scheuer T, Catterall WA (2013) Synergistic GABA-enhancing therapy against seizures in a mouse model of Dravet syndrome. J Pharmacol Exp Ther 345:215–224. doi:10.1124/jpet.113.203331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kalume F, Westenbroek RE, Cheah CS, Yu FH, Oakley JC, Scheuer T, Catterall WA (2013) Sudden unexpected death in a mouse model of Dravet syndrome. J Clin Invest 123:1798–1808. doi:10.1172/JCI66220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cheah CS, Yu FH, Westenbroek RE, Kalume FK, Oakley JC, Potter GB, Rubenstein JL, Catterall WA (2012) Specific deletion of NaV1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome. Proc Natl Acad Sci USA 109:14646–14651. doi:10.1073/pnas.1211591109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kalume F, Westenbroek RE, Cheah CS, Oakley JC, Scheuer T, Catterall WA (2013) Sudden unexpected death in a mouse model of Dravet Syndrome. J Clin Invest. doi:10.1172/JCI66220

    PubMed  PubMed Central  Google Scholar 

  74. Dravet C (2003) Dravet’s syndrome (severe myoclonic epilepsy in infancy). http://www.ilae-epilepsy.org/ctf/dravet.html

  75. Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O (2005) Severe myoclonic epilepsy in infancy: Dravet syndrome. Adv Neurol 95:71–102

    PubMed  Google Scholar 

  76. Kalume F, Yu FH, Westenbroek RE, Scheuer T, Catterall WA (2007) Reduced sodium current in Purkinje neurons from Nav1.1 mutant mice: implications for ataxia in severe myoclonic epilepsy in infancy. J Neurosci 27:11065–11074. doi:10.1523/JNEUROSCI.2162-07.2007

    Article  CAS  PubMed  Google Scholar 

  77. Nolan KJ, Camfield CS, Camfield PR (2006) Coping with Dravet syndrome: parental experiences with a catastrophic epilepsy. Dev Med Child Neurol 48:761–765. doi:10.1017/S0012162206001629

    Article  PubMed  Google Scholar 

  78. Han S, Yu FH, Schwartz MD, Linton JD, Bosma MM, Hurley JB, Catterall WA, de la Iglesia HO (2012) NaV1.1 channels are critical for intercellular communication in the suprachiasmatic nucleus and for normal circadian rhythms. Proc Natl Acad Sci USA 109:E368–E377. doi:10.1073/pnas.1115729109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kalume F, Oakley JC, Westenbroek RE, Gile J, de la Iglesia HO, Scheuer T, Catterall WA (2015) Sleep impairment and reduced interneuron excitability in a mouse model of Dravet syndrome. Neurobiol Dis. 77:141–154. doi:10.1016/j.nbd.2015.02.016

    Article  PubMed  PubMed Central  Google Scholar 

  80. Han S, Tai C, Westenbroek RE, Yu FH, Cheah CS, Potter GB, Rubenstein JL, Scheuer T, de la Iglesia HO, Catterall WA (2012) Autistic-like behaviour in Scn1a +/− mice and rescue by enhanced GABA-mediated neurotransmission. Nature 489:385–390. doi:10.1038/nature11356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Rudy B, Fishell G, Lee S, Hjerling-Leffler J (2011) Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons. Dev Neurobiol 71:45–61. doi:10.1002/dneu.20853

    Article  PubMed  PubMed Central  Google Scholar 

  82. Rubinstein M, Han S, Tai C, Westenbroek RE, Hunker A, Scheuer T, Catterall WA (2015) Dissecting the phenotypes of Dravet syndrome by gene deletion. Brain 138:2219–2233. doi:10.1093/brain/awv142

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The work on sodium channels from my laboratory has depended on many outstanding colleagues—graduate students, postdoctoral fellows, and research technicians. Without their insight, hard work, dedication, and professionalism, we would not have made significant advances. Our work also has depended on the continuous support of research grants from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung, and Blood Institute of the National Institutes of Health. Their generous support made this research on sodium channels possible, as well as most other advances in biomedical sciences in the US.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Washington, Seattle, WA, 98195-7280, USA

    William A. Catterall

Authors
  1. William A. Catterall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William A. Catterall.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Catterall, W.A. Forty Years of Sodium Channels: Structure, Function, Pharmacology, and Epilepsy. Neurochem Res 42, 2495–2504 (2017). https://doi.org/10.1007/s11064-017-2314-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-017-2314-9

Keywords

Search

Navigation