Mechanisms of sodium channel inactivation

Current Opinion in Neurobiology

Volumn 13, Issue 3, 2003, Pages 284-290

  Goldin, Alan L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SODIUM CHANNEL;

BETA CHAIN; CARBOXY TERMINAL SEQUENCE; CENTRAL NERVOUS SYSTEM; CHANNEL GATING; ELECTRIC ACTIVITY; EPILEPSY; EXCITABILITY; GENE INACTIVATION; HEART REPOLARIZATION; HEART VENTRICLE FIBRILLATION; HUMAN; LONG QT SYNDROME; NONHUMAN; PRIORITY JOURNAL; REVIEW;

EID: 0038721687     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(03)00065-5     Document Type: Review

References (67)

1. Catterall W.A. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron. 26:2000;13-25.
2. Raman I.M., Bean B.P. Inactivation and recovery of sodium channels in cerebellar Purkinje neurons: evidence for two mechanisms. Biophys. J. 80:2001;729-737 Recovery from inactivation in cerebellar Purkinje neurons is unusual in that it is accompanied by a significant ionic current. The authors suggest a model to explain this phenomenon that postulates that there are two mechanisms of inactivation. The conventional process involves the III-IV linker inactivating particle occluding the pore. A novel process involves a voltage-dependent block by another particle that can enter and exit only when the channel is open, so that current flows during recovery.
3. v1.6. The authors suggest that the resurgent current may result from the alternative inactivation process, and they find that it requires constitutive phosphorylation.
4. Cummins T.R., Aglieco F., Renganathan M., Herzog R.I., Dib-Hajj S.D., Waxman S.G. Nav1.3 sodium channels: rapid repriming and slow closed-state inactivation display quantitative differences after expression in a mammalian cell line and in spinal sensory neurons. J. Neurosci. 21:2001;5952-5961.
5. Rohl C.A., Boeckman F.A., Baker C., Scheuer T., Catterall W.A., Klevit R.E. Solution structure of the sodium channel inactivation gate. Biochemistry. 38:1999;855-861.
6. Kuroda Y., Miyamoto K., Matsumoto M., Maeda Y., Kanaori K., Otaka A., Fujii N., Nakagawa T. Structural study of the sodium channel inactivation gate peptide including an isoleucine-phenylalanine-methionine motif and its analogous peptide (phenylalanine/glutamine) in trifluoroethanol solutions and SDS micelles. J. Pept. Res. 56:2000;172-184.
7. Miyamoto K., Nakagawa T., Kuroda Y. Solution structure of the cytoplasmic linker between domain III-S6 and domain IV-S1 (III-IV linker) of the rat brain sodium channel in SDS micelles. Biopolymers. 59:2001;380-393.
8. Miyamoto K., Kanaori K., Nakagawa T., Kuroda Y. Solution structures of the inactivation gate particle peptides of rat brain type-IIA and human heart sodium channels in SDS micelles. J. Pept. Res. 57:2001;203-214.
9. 5 (S4-S5) in domains III and IV of human brain sodium channels in SDS micelles. J. Pept. Res. 58:2001;193-203.
10. + channel probed by cysteine mutagenesis. J. Physiol. (Lond.). 505:1997;345-352.
11. Filatov G.N., Nguyen T.P., Kraner S.D., Barchi R.L. Inactivation and secondary structure in the D4/S4-5 region of the SkM1 sodium channel. J. Gen. Physiol. 111:1998;703-715.
12. Smith M.R., Goldin A.L. Interaction between the sodium channel inactivation linker and domain III S4-S5. Biophys. J. 73:1997;1885-1895.
13. McPhee J.C., Ragsdale D.S., Scheuer T., Catterall W.A. A critical role for the S4-S5 intracellular loop in domain IV of the sodium channel α-subunit in fast inactivation. J. Biol. Chem. 273:1998;1121-1129.
14. Sirota F.L., Pascutti P.G., Anteneodo C. Molecular modeling and dynamics of the sodium channel inactivation gate. Biophys. J. 82:2002;1207-1215 The authors use theoretical modeling and molecular dynamic simulations to predict the structure of the III-IV linker inactivating particle. They propose that there are two α-helical segments followed by a hairpin motif, with the hairpin being responsible for long-range interactions that facilitate the movement of the IFM motif towards its docking site.
15. + channels. J. Gen. Physiol. 109:1997;607-617.
16. + channel during gating. Neuron. 16:1996;859-867.
17. Ong B.-H., Tomaselli G.F., Balser J.R. A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence. J. Gen. Physiol. 116:2000;653-661.
18. + channels. J. Gen. Physiol. 120:2002;509-516 The authors show that modification of engineered cysteine residues in the P regions of all four domains demonstrate no difference in accessibility following slow inactivation, suggesting that the outer mouth of the pore remains open.
19. Mitrovic N., George A.L. Jr., Horn R. Role of domain 4 in sodium channel slow inactivation. J. Gen. Physiol. 115:2000;707-717.
20. v1.5. These results suggest that the kinetics of slow inactivation are regulated by residues that are outside of the P regions.
21. O'Reilly J.P., Wang S.-Y., Wang G.K. Residue-specific effects on slow inactivation at V787 in D2-S6 of Nav1.4 sodium channels. Biophys. J. 81:2001;2100-2111.
22. Hilber K., Sandtner W., Kudlacek O., Glaaser I.W., Weisz E., Kyle J.W., French R.J., Fozzard H.A., Dudley S.C. Jr., Todt H. The selectivity filter of the voltage-gated sodium channel is involved in channel activation. J. Biol. Chem. 276:2001;27831-27839.
23. Hilber K., Sandtner W., Kudlacek O., Schreiner B., Glaaser I., Schütz W., Fozzard H.A., Dudley S.C. Jr., Todt H. Interaction between fast and ultra-slow inactivation in the voltage-gated sodium channel. Does the inactivation gate stabilize the channel structure. J. Biol. Chem. 277:2002;37105-37115 The authors show that ultra-slow inactivation is enhanced by a single amino acid substitution in the P region of domain IV. This process is accompanied by a rearrangement of the outer vestibule, and it is inhibited by binding of the fast inactivation particle in the inner vestibule.
24. Deschênes I., Trottier E., Chahine M. Implication of the C-terminal region of the α-subunit of voltage-gated sodium channels in fast inactivation. J. Membr. Biol. 183:2001;103-114.
25. Mantegazza M., Yu F.H., Catterall W.A., Scheuer T. Role of the C-terminal domain in inactivation of brain and cardiac sodium channels. Proc. Natl. Acad. Sci. USA. 98:2001;15348-15353.
26. + channel. Circulation. 99:1999;3165-3171.
27. Deschênes I., Baroudi G., Berthet M., Barde I., Chalvidan T., Denjoy I., Guicheney P., Chahine M. Electrophysiological characterization of SCNA mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes. Cardiovasc. Res. 46:2000;55-65.
28. + channel C terminus. Evidence for a role of helical structures in modulation of channel inactivation. J. Biol. Chem. 277:2002;9233-9241 The authors find that homology modeling and circular dichroism of the carboxy-terminus predicts six α helices in the proximal half with little structure in the distal half. Deletion of the distal half reduces sodium current density but does not affect gating. In contrast, a deletion that includes the sixth helix reduces current density and delays inactivation by shifting gating into a bursting mode. It is proposed that charged residues in the sixth helix stabilize the inactivated state.
29. 1 subunit. J. Gen. Physiol. 120:2002;887-895.
30. 1 subunit: a deletion analysis. Pflugers Arch. 431:1995;186-195.
31. + channel function in the extracellular domain of the β1 subunit. J. Biol. Chem. 273:1998;3954-3962.
32. McCormick K.A., Srinivasan J., White K., Scheuer T., Catterall W.A. The extracellular domain of the β1 subunit is both necessary and sufficient for β1-like modulation of sodium channel gating. J. Biol. Chem. 274:1999;32638-32646.
33. Stevens E.B., Cox P.J., Shah B.S., Dixon A.K., Richardson P.J., Pinnock R.D., Lee K. Tissue distribution and functional expression of the human voltage-gated sodium channel β3 subunit. Pflugers Arch. 441:2001;481-488.
34. Shah B.S., Stevens E.B., Pinnock R.D., Dixon A.K., Lee K. Developmental expression of the novel voltage-gated sodium channel auxiliary subunit β3, in rat CNS. J. Physiol. (Lond.). 534:2001;763-776.
35. Qu Y., Curtis R., Lawson D., Gilbride K., Ge P., Distefano P.S., Silos-Santiago I., Catterall W.A., Scheuer T. Differential modulation of sodium channel gating and persistent sodium currents by the β1, β2, and β3 subunits. Mol. Cell Neurosci. 18:2001;570-580 The authors find that all three β subunits shift sodium channel activation and inactivation to more positive potentials in tsA-201 cells, but that the β3 subunit is unique in causing increased persistent current. The β3 subunit is expressed broadly in the CNS and PNS, and its association with the α subunit should increase electrical excitability.
36. Meadows L.S., Chen Y.H., Powell A.J., Clare J.J., Ragsdale D.S. Functional modulation of human brain Nav1.3 sodium channels, expressed in mammalian cells, by auxiliary β1, β2 and β3 subunits. Neuroscience. 114:2002;745-753.
37. Fahmi A.I., Patel M., Stevens E.B., Fowden A.L., John J.E. III, Lee K., Pinnock R., Morgan K., Jackson A.P., Vandenberg J.I. The sodium channel β-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J. Physiol. (Lond.). 537:2001;693-700.
38. Chen C., Bharucha V., Chen Y., Westenbroek R.E., Brown A., Malhotra J.D., Jones D., Avery C., Gillespie P.J. III, Kazen-Gillespie K.A.et al. 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. 99:2002;17072-17077 The authors created knockout mice that lacked the β2 subunit, and found that they are viable but demonstrate reduced sodium channel density, as evidenced by both electrophysiological recording and saxitoxin binding, with an increased threshold for action potential generation. The mice displayed increased susceptibility to seizures but no other neurological abnormalities.
39. Isom L.L., DeJongh K.S., Catterall W.A. Auxiliary subunits of voltage-gated ion channels. Neuron. 12:1994;1183-1194.
40. Cannon S.C. Spectrum of sodium channel disturbances in the nondystrophic myotonias and periodic paralyses. Kidney Int. 57:2000;772-779.
41. Balser J.R. Inherited sodium channelopathies: models for acquired arrhythmias? Am. J. Physiol. Heart Circ. Physiol. 282:2002;H1175-H1180.
42. +-channel β1 subunit gene SCN1B. Nat. Genet. 19:1998;366-370.
43. Escayg A., MacDonald B.T., Meisler M.H., Baulac S., Huberfeld G., An-Gourfinkel I., Brice A., LeGuern E., Moulard B., Chaigne D.et al. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nat. Genet. 24:2000;343-345.
44. Vilin Y.Y., Fujimoto E., Ruben P.C. A novel mechanism associated with idiopathic ventricular fibrillation (IVF) mutations R1232W and T1620M in human cardiac sodium channels. Pflugers Arch. 442:2001;204-211.
45. + channel associated with idiopathic ventricular fibrillation. Am. J. Physiol. Heart Circ. Physiol. 280:2001;H354-H360.
46. Rivolta I., Abriel H., Tateyama M., Liu H., Memmi M., Vardas P., Napolitano C., Priori S.G., Kass R.S. Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J. Biol. Chem. 276:2001;30623-30630.
47. + channel. Circ. Res. 86:2000;e91-e97.
48. Wallace R.H., Scheffer I.E., Parasivam G., Barnett S., Wallace G.B., Sutherland G.R., Berkovic S.F., Mulley J.C. Generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN1B. Neurology. 58:2002;1426-1429.
49. Escayg A., Heils A., MacDonald B.T., Haug K., Sander T., Meisler M.H. A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus and prevalence of variants in patients with epilepsy. Am. J. Hum. Genet. 68:2001;866-873.
50. v1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc. Natl. Acad Sci. USA. 98:2001;6384-6389.
51. v1.1 mutations cause febrile seizures associated with afebrile partial seizures. Neurology. 57:2001;703-705.
52. Wallace R.H., Scheffer I.E., Barnett S., Richards M., Dibbens L., Desai R.R., Lerman-Sadie T., Lev D., Mazarib A., Brand N.et al. Neuronal sodium-channel α1-subunit mutations in generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet. 68:2001;859-865.
53. Abou-Khalil B., Ge Q., Desai R., Ryther R., Bazyk A., Bailey R., Haines J.L., Sutcliffe J.S., George A.L. Jr. Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation. Neurology. 57:2001;2265-2272.
54. Claes L., Del-Favero J., Cuelemans B., Lagae L., Van Broeckhoven C., De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am. J. Hum. Genet. 68:2001;1327-1332.
55. Sugawara T., Mazaki-Miyazaki E., Fukushima K., Shimomura J., Fujiwara T., Hamano S., Inoue Y., Yamakawa K. Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy. Neurology. 58:2002;1122-1124.
56. Moran O., Conti F. Skeletal muscle sodium channel is affected by an epileptogenic β1 subunit mutation. Biochem. Biophys. Res. Commun. 282:2001;55-59.
57. Tammaro P., Conti F. Moran O, Modulation of sodium current in mammalian cells by an epilepsy-correlated β1-subunit mutation. Biochem. Biophys. Res. Commun. 291:2002;1095-1101.
58. Meadows L.S., Malhotra A., Loukas A., Thyagarajan V., Kazen-Gillespie K.A., Koopmann M.C., Kriegler S., Isom L.L., Ragsdale D.S. Functional and biochemical analysis of a sodium channel β1 subunit mutation responsible for generalized epilepsy with febrile seizures plus type 1. J. Neurosci. 22:2002;10699-10709 The authors find that the mutant β1 subunit that causes GEFS+1 increases sodium channel availability at hyperpolarized potentials and reduces current rundown during high frequency depolarizations compared to the wild-type β1 subunit. The mutation also disrupts homophilic cell adhesion, but it does not function as a dominant negative subunit.
59. Spampanato J., Escayg A., Meisler M.H., Goldin A.L. Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2. J. Neurosci. 21:2001;7481-7490 The authors find that two α subunit mutations that cause GEFS+2 have different effects on sodium channel activity in Xenopus oocytes. R1648H in IVth domain S4 accelerates recovery from inactivation and reduces current rundown during high frequency depolarizations, which should increase electrical excitability. In contrast, T875M in II S4 enhances slow inactivation, thus decreasing channel availability and electrical excitability.
60. Alekov A.K., Rahman M., Mitrovic N., Lehmann-Horn F., Lerche H. Enhanced inactivation and acceleration of activation of the sodium channel associated with epilepsy in man. Eur. J. Neurosci. 13:2001;2171-2176.
61. v1.1 sodium channels. Neuroscience. 116:2003;37-48.
62. Alekov A.K., Rahman M.M., Mitrovic N., Lehmann-Horn F., Lerche H. A sodium channel mutation causing epilepsy in man exhibits defects in fast inactivation and inactivation in vitro. J. Physiol. (Lond.). 529:2000;533-539.
63. v1.1 cDNA clone was constructed, expressed in tsA-201 cells, and used to study three mutations that cause GEFS+2. The authors found that R1648H increased persistent current to approximately 4% and T875M and W1204R increased persistent current to 1-2%.
64. v1.2 mutant channel with slowed inactivation and increased persistent current, and found that they showed seizure activity and had a shortened life span. Electroencephalographic recordings demonstrated focal seizures in the hippocampus, with generalization to the cortex in some cases.
65. Bendahhou S., Cummins T.R., Hahn A.F., Langlois S., Waxman S.G., Ptácek L.J. A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. J. Clin. Invest. 106:2000;431-438.
66. Struyk A.F., Scoggan K.A., Bulman D.E., Cannon S.C. The human skeletal muscle Na channel mutation R669H associated with hypokalemic periodic paralysis enhances slow inactivation. J. Neurosci. 20:2000;8610-8617.
67. Jurkat-Rott K., Mitrovic N., Hang C., Kouzmekine A., Iaizzo P., Herzog J., Lerche H., Nicole S., Vale-Santos J., Chauveau D.et al. Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proc. Natl. Acad Sci. USA. 97:2000;9549-9554.