Abstract
Slow inactivation in voltage-gated sodium channels is a biophysical process that governs the availability of sodium channels over extended periods of time. Slow inactivation, therefore, plays an important role in controlling membrane excitability, firing properties, and spike frequency adaptation. Defective slow inactivation is associated with several diseases of cell excitability, such as hyperkalemic periodic paralysis, myotonia, idiopathic ventricular fibrillation and long-QT syndrome. These associations underscore the physiological importance of this phenomenon. Nevertheless, our understanding of the molecular substrates for slow inactivation is still fragmentary. This review covers the current state of knowledge concerning the molecular underpinnings of slow inactivation, and its relationship with other biophysical processes of voltage-gated sodium channels.
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Rogart, R. B., Cribbs, L. L., Muglia, L. K., Kephart, D. D., and Kaiser, M. W. (1989) Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform, Proc. Natl. Acad. Sci. 86, 8170–8174.
Trimmer, J., Cooperman, S., Tomiko, S., Zhou, J., Crean, S., Boyle, M., et al. (1989) Primary structure and functional expression of a mammalian skeletal muscle sodium channel. Neuron 3, 33–49.
George, A. L., Komisarof, J., Kallen, R. G., and Barchi, R. L. (1992) Primary structure of the adult human skeletal muscle voltage-dependent sodium channel, Ann. Neurol. 31, 313–337.
Gellens, M. E., George, A. L., Jr., Chen, L., Chahine, M., Horn, R., Barchi, R. L., and Kallen, R. G. (1992) Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc. Natl. Acad. Sci. 89, 554–558.
Fozzard, H. A. and Hanck, D. A. (1996) Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms, Physiol. Rev. 76, 887–926.
Isom, L. L., DeJongh, K. S., and Catterall, W. A. (1994) Auxiliary subunits of voltage-gated ion channels, Neuron 12, 1183–1194.
Sato, C., Sato, M., Iwasaki, A., Doi, T., and Engel, A. (1998) The sodium channel has four domains surrounding a central pore, J. Struct. Biol. 121, 314–325.
Guy, H. R. and Conti, F. (1990) Pursuing the structure and function of voltage-gated channels. Trends Neurosci. 13, 201–206.
Guy, H. R. and Durell, S. R. (1994) Using sequence homology to analyze the structure and function of voltage-gated ion channel proteins. Soc. Gen. Physiol. Ser. 49, 197–212.
Catterall, W. A. (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26, 13–25.
Marban, E., Yamagishi, T., and Tomaselli, G. F. (1998) Structure and function of voltage-gated sodium channels, J. Physiol. (London) 508, 647–657.
Ji, S., George, A. L., Horn, R., and Barchi, R. L. (1996) Paramyotonia congenita mutations reveal different roles for segments S3 and S4 of domain D4 in hSkM1 sodium channel gating. J. Gen. Physiol. 107, 183–194.
Kontis, K. J., Rounaghi, A., and Goldin, A. L. (1997) Sodium channel activation gating is affected by substitutions of voltage sensor positive charges in all four domains, J. Gen. Physiol. 110, 391–401.
Cha, A., Ruben, P. C., George, A. L., Fujimoto, E., and Bezanilla, F. (1999) Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation. Neuron 22, 73–87.
Groome, J. R., Fujimoto, E., George, A. L., and Ruben, P. C. (1999) Differential effects of homologous S4 mutations in human skeletal muscle sodium channels on deactivation gating from open and inactivated states, J. Physiol. 516, 687–698.
Groome, J. R., Fujimoto, E., and Ruben, P. C. (2000) The delay in recovery from fast inactivation in skeletal muscle sodium channels is deactivation, Cell Mol. Neurobiol. 20, 521–527.
Kontis, K. J. and Goldin, A. L. (1997) Sodium channel inactivation is altered by substitution of voltage sensor positive charges, J. Gen. Physiol. 110, 403–413.
Mitrovic, N., George, A. L., Jr., and Horn, R. (1998) Independent versus coupled inactivation in sodium channels: Role of the domain 2 S4 segment, J. Gen. Physiol. 111, 451–462.
Mitrovic, N., George, A. L., Jr., and Horn, R. (2000) Role of domain 4 in sodium channel slow inactivation, J. Gen. Physiol. 115, 707–717.
Goldin, A. L. (1993) Accessory subunits and sodium channel inactivation, Curr. Opin. Neurobiol. 3, 272–277.
Goldin, A., Barchi, R., Caldwell, J., Hofman, F., Howe, J., Hunter, J., et al. (2000) Nomenclature of voltage-gated sodium channels, Neuron 271, 15,950–15,962.
Catterall, W. A. (1993) Structure and function of voltage-gated ion channels, Trends Neurosci. 16, 500–506.
Nuss, H. B., Chiamvimonvat, N., Perez-Garcia, M. T., Tomaselli, G. F., and Marban, E. (1995) Functional association of the β1 subunit with human cardiac (hH1) and rat skeletal muscle (μ1) sodium channel α subunits expressed in Xenopus oocytes, J. Gen. Physiol. 106, 1171–1191.
Makielski, J. C., Limberis, J. T., Chang, S. Y., Fan, Z., and Kyle, J. W. (1996) Coexpression of β1 with cardiac sodium channel α-subunits in oocytes decreases lidocaine block, Mol. Pharm. 49, 30–39.
Isom, L. L., Jongh, K. S. D., Patton, D. E., Reber, B. F. X., Offord, J., Charbonneau, H., et al. (1992) Primary structure and functional expression of the β1 subunit of the rat brain sodium channel, Science 256, 839–842.
Chen, C. and Cannon, S. C. (1995) Modulation of Na+ channel inactivation by the β1 subunit: a deletion analysis, Pflugers Arch. 431, 186–195.
Yang, J. S., Bennett, P. B., Makita, N., George, A. L., Jr., and Barchi, R. L. (1993) Expression of the sodium channel β1 subunit in rat skeletal muscle is selectively associated with the tetrodotoxin-sensitive α-subunit isoform. Neuron 11, 915–922.
Patton, D., Isom, L. L., Catterall, W. A., and Goldin, A. L. (1994) The adult rat brain β1 subunit modifies activation and inactivation gating of multiple sodium channel α subunits, J. Biol. Chem. 269, 17649–17655.
Makita, N., Bennett, P. B., and George, A. L. (1994) Voltage-gated Na+ channel β1 subunit mRNA expressed in adult human skeletal musole, heart and brain is encoded by a single gene, J. Biol. Chem. 269, 7571–7578.
McCormick, K. A., Isom, L. I., Ragsdales, D., Smith, D., Scheuer, T., and Catterall, W. (1998) Molecular determinants of Na+ channel function in the extracellular domain of β1 subunit. J. Biol. Chem. 273, 3954–3962.
Featherstone, D. E., Richmond, J. E., and Ruben, P. C. (1996) Interaction between fast and slow inactivation in Skm1 sodium channels. Biophys. J. 71, 3098–3109.
O'Reilly, J. P., Wang, S. Y., Kallen, R. G., and Wang, G. K. (1999) Comparison of slow inactivation in human heart and rat skeletal muscle Na+ channel chimaeras, J. Physiol. 515, 61–73.
Vilin, Y. Y., Fujimoto, E., and Ruben, P. C. (2001) A single residue differentiates between human cardiac and skeletal muscle Na+ channel slow inactivation. Biophys. J. 80, 2221–2230.
Richmond, J. E., Featherstone, D. E., Hartmann, H. A., and Ruben, P. C. (1998) Slow inactivation in human cardiac sodium channels. Biophys. J. 74, 2945–2952.
Toib, A., Lyakhov, V., and Marom, S. (1998) Interaction between duration of activity and time course of recovery from slow inactivation in mammalian brain Na+ channels, J. Neurosc. 18, 1893–1903.
Ellerkmann, R. K., Riazanski, V., Elger, C. E., Urban, B. W., and Beck, H. (2001) Slow recovery from inactivation regulates the availability of voltage-dependent-dependent dependent Na+ channels in hippocampal granule cells, hilar neurons and basket cells, J. Physiol. (London) 532, 385–397.
Veldkamp, M. W., Viswanathan, P. C., Bezzina, C., Baartscheer, A., Wilde, A. A. M., and Balser, J. R. (2000) Two distinct congential arrhythmias evoked by a multidysfunctional Na+ channel, Circ. Res. 86, e91-e97.
Kambouris, N. G., Hastings, L. A., Stepanovic, S., Marban, E., Tomaselli, G. F., and Balser, J. R. (1998) Mechanistic link between lidocaine block and inactivation probed by outer pore mutations in the rat μ1 skeletal muscle sodium channel, J. Physiol. 512, 693–705.
Todt, H., Dudley, S. C., Kyle, J. W., French, R. J., and Fozzard, H. A. (1999) Ultra-slow inactivation in μ1 Na+ channels is produced by a structural rearrangement of the outer vestibule. Biophys. J. 76, 1335–1345.
Hilbert, K., Sandtner, Kudlacek, O., Glaaser, I. W., Weisz, E., Kyles, J. W., et al. (2001) The selectivity filter of the voltage-gated sodium channel is involved in channels activation, J. Biol. Chem. 276, 27,831–27,839.
Vilin, Y. Y., Makita, N., George, A. L., Jr., and Ruben, P. C. (1999) Structural determinants of slow inactivation in human cardiac and skeletal muscle sodium channels. Biophys. J. 77, 1384–1393.
Sawczuk, A., Powers, R. K., and Binder, M. C. (1995) Spike frequency adaptation studied in hypoglossal motoneurons of the rat, J. Neurophysiol. 73, 1799–1810.
Chang, S. Y., Satin, J., and Fozzard, H. A. (1996) Modal behavior of the μ1 Na+ channel and effects of co-expression of the β1-subunit. Biophys. J. 70, 2581–2592.
Fleig, A., Ruben, P. C., and Rayner, M. D. (1994) Kinetic mode switch of rat brain IIA Na channels in Xenopus oocytes excised macropatches, Pflugers Arch. 427, 399–405.
Hebert, T. E., Monette, R., Dunn, R. J., and Drapeau, P. (1994) Voltage dependencies of the fast and slow gating models of RIIA sodium channels. Proceedings of the Royal Society of London 256, 253–261.
Schreibmayer, W., Wallner, M., and Lotan, I. (1994) Mechanism of modulation of single sodium channels from skeletal muscle by the β1-subunit from rat brain. Pflugers Arch. 426, 360–362.
Moorman, J. R., Kirsch, G. E., Brown, A. M., and Joho, R. H. (1990) Changes in sodium channel gating produced by point mutations in a cytoplasmic linker. Science 250, 688–691.
Zhou, J., Potts, J. F., Trimmer, J. S., Agnew, W. S., and Sigworth, F. J. (1991) Multiple gating modes and the effect of modulating factors on the microliter sodium channel. Neuron 7, 775–785.
Cannon, S. C., Brown R. H., Jr., and Corey, D. P. (1991) A sodium channel defect in hyperkalemic periodic paralysis: potassium-induced failure of inactivation. Neuron 6, 619–626.
Lehmann-Horn, F. and Jurkat-Rott, K. (1999) Voltage-gated ion channels and hereditary disease. Physiol. Rev. 79, 1317–1372.
Ptacek, L. J., Trimmer, J. S., Agnew, W. S., Roberts, J. W., Petajan, J. H., and Leppert, M. (1991) Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus. Am. J. Hum. Gen. 49, 851–854.
Townsend, C. and Horn, R. (1997) Effect of alkali metal cations on slow inactivation of cardiac Na+ channels. J. Gen. Physiol. 110, 23–33.
Cummins, T. R. and Sigworth, F. J. (1996) Impaired slow inactivation in mutant sodium channels. Biophys. J. 71, 227–236.
Hayward, L., Brown, R., and Cannon, S. (1997) Slow inactivation differs among mutant Na+ channels associated with myotonia and periodic paralysis. Biophys. J. 72, 1204–1219.
Rudy, B. (1978) Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance. J. Physiol. (London) 283, 1–21.
Starkus, J. G. and Shrager, P. (1978) Modification of slow sodium inactivation in nerve after internal perfusion with trypsin. Am. J. Physiol., 235, C238-C244.
Valenzuela, C. and Bennett, P. B. (1994) Gating of cardiac Na+ channels in excised membrane patches after modification by α-chymotrypsin. Biophys. J. 67, 161–171.
Salgado, V. L., Yeh, J. Z., and Narahashi, T. (1985) Voltage-dependent removal of sodium channel inactivation by N-bromoacetamide and pronase. Biophys. J. 47, 567–571.
Hille, B. (1992) Ionic Channels of Excitable Membranes. Sinauer Associates, Sunderland, Massachusetts.
Ruff, R. L., Simoncini, L., and Stuhmer, W. (1988) Slow sodium channel inactivation in mammalian muscle: a possible role in regulating excitability. Muscle and Nerve 11, 502–510.
Wang, S. and Wang, G. K. (1997) A mutation in segment I-S6 alters slow inactivation of sodium channels. Biophys. J. 72, 1633–1640.
West, J. W., Patton, D. E., Scheuer, T., Wang, Y., Goldin, A. L., and Catterall, W. A. (1992) A cluster of hydrophobic amino acid residues required for fast Na+ channel inactivation. Proc. Natl. Acad. Sci. 89, 10910–10914.
Vedantham, V. and Cannon, S. C. (1998) Slow inactivation does not affect movement of the fast inactivation gate in voltage-gated Na+ channels. J. Gen. Physiol. 111, 83–93.
Ruben, P. C., Starkus, J. G., and Rayner, M. D. (1992) Steady-state availability of sodium channels. Interactions between activation and slow inactivation. Biophys. J. 61, 941–955.
Patton, D. E., West, J. W., Catterall, W. A., and Goldin, A. L. (1992) Amino acid residues required for fast Na+ channel inactivation: charge neutralizations and deletions in the III–IV linker. Proc. Natl. Acad. Sci. 89, 10905–10909.
Bezanilla, F., Taylor, R. E., and Fernandez, J. M. (1982) Distribution and kinetics of membrane dielectric polarization. 1. Long-term inactivation of gating currents. J. Gen. Physiol. 79, 21–40.
Rayner, M. D. and Starkus, J. G. (1989) The steady-state distribution of gating charge in crayfish giant axons. Biophys. J. 55, 1–19.
Zagotta, W. N., Hoshi, T., and Aldrich, R. W. (1990) Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB. Science 250, 568–571.
Yellen, G., Sodickson, D., Chen, T. Y., and Jurman, M. E. (1994) An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding. Biophys. J. 66, 1068–1075.
Liu, Y., Jurman, M. E., and Yellen, G. (1996) Dynamic rearrangement of the outer mouth of a K+ channel during gating. Neuron 16, 859–867.
Kiss, L., LoTurco, J., and Korn, S. J. (1999) Contribution of the selectivity filter to inactivation in potassium channels. Biophys. J. 76, 253–263.
Loots, E. and Isacoff, E. Y. (1998) Protein rearrangements underlying slow inactivation of the Shaker K+ channel. J. Gen. Physiol. 112, 377–389.
Boland, L. M., Juraman, M. E., and Yellen, G. (1994) Cysteines in the Shaker K+ channel are not essential for channel activity or zinc modulation. Biophys. J. 66, 694–699.
Cha, A. and Bezanilla, F. (1997) Characterizing voltage-dependent conformational changes in the Shaker K+ channel with fluorescence. Neuron 19, 1127–1140.
Loots, E. and Isacoff, E. Y. (2000) Molecular coupling of S4 to a K+ channel's slow inactivation gate. J. Gen. Physiol. 116, 623–635.
Ruff, R. L. (1996) Single-channel basis of slow inactivation of Na+ channels in rat skeletal muscle. Am. J. Physiol. 271, C971–981.
Sheets, M. F., Kyle, J. W., and Hanck, D. A. (2000) The role of the putative inactivation lid in sodium channel gating current immobilization. J. Gen. Physiol. 115, 609–619.
Struyk, A. F., Scoggan, K. A., Bulman, D. E., and Cannon, S. C. (2000) The human skeletal muscle Na+ channel mutation R669H associated with hypokalemic periodic paralysis enhances slow inactivation. J. Neurosci. 20, 8610–8617.
Cannon, S. C. (1996) Ion-channel defects and aberrant excitability in myotonia and periodic paralysis. Trends Neurosci. 19, 3–10.
Cannon, S. C., Brown, R.H., Jr., and Corey, D. P. (1993) Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels. Biophys. J. 65, 270–288.
Hayward, L. L., Brown, R. H., Jr., and Cannon, S. C. (1996) Inactivation defects caused by myotonia-associated mutations in the sodium channel III–IV linker. J. Gen. Physiol. 107, 559–576.
Cannon, S. C. and Strittmatter, S. M. (1993) Functional expression of sodium channel mutations identified in families with periodic paralysis. Neuron 10, 317–326.
Ruff, R. L. (1994) Slow Na+ channel inactivation must be disrupted to evoke prolonged depolarization-induced paralysis. Biophys. J. 66, 542–545.
Ptacek, L. J., George, A. L., Griggs, R. C., Tawil, R., Kallen, R. G., Barchi, R. L., et al. (1991) Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell 67, 1021–1027.
Yang, N., Ji, S., Zhou, M., Ptacek, L. J., Barchi, R. L., Korn, R., and George, A. L. (1994) Sodium channel mutations in paramyotonia congenita exhibit similar biophysical phenotypes in vitro. Proc. Natl. Acad. Sci. 91, 12,785–12,789.
Hayward, L. J., Sandoval, G. M., and Cannon, S. C. (1999) Defective slow inactivation of sodium channels contributes to familial periodic paralysis. Neurology 52, 1447–53.b
Bendahhou, S., Cummins, T. R., Hahn, A. F., Langlois, S., Waxman, S. G., and Ptacek, L. J. (2000) A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation. J. Clin. Invest. 106, 431–438.
Bendahhou, S., Cummins, T. R., Tawil, R., Waxman, S. G., and Ptacek, L. J. (1999) Activation and inactivation of the voltage-gated sodium channel: role of segment S5 revealed by a novel hyperkalaemic periodic paralysis mutation. J. Neurosci. 19, 4762–4771.
Takahashi, M. P. and Cannon, S. C. (1999) Enhanced slow inactivation by V445M: A sodium channel mutation associated with myotonia. Biophys. J., 76, 861–868.
Wang, Q., Shen, J., Spalwski, I., Robinson, J. L., Moss, A. J., Towbin, J. A., and Keating, M. T. (1995) SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80, 805–811.
Bezzina, C., Veldkamp, M. W., Berg, M. P., Postma, A. V., Rook, M. B., Viersma, J.-W., et al. E., (1999) A single Na+ channel mutation causing both long-QT and Brugada syndromes. Circ. Res. 85, 1206–1213.
Gussak, I., Antzelevitch, C., Bjerregaard, P., Towbin, J. A., and Chaitman, B. R. (1999) The Brugada syndrome: clinical, electrophysiological and genetic aspects. J. Am. Coll. Cardiol. 33, 5–15.
Corrado, D., Buja, G., Basso, C., Nava, A., and Thiene, G. (1999) What is the Brugada syndrome? Cardiology in review 7, 191–195.
Antzelevitch, C. (1999) Ion channels and ventricular arrhythmias: cellular and ionic mechanisms underlying the Brugada syndrome. Curr. Opin. Cardiol. 14, 274–279.
Brugada, P. and Brugada, J. (1992) Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. J. Am. Coll. Cardiol. 20, 1391–1396.
Schwartz, P. J., Locati, E. H., Napolitano, C., and Priori, S. G. (1995) The long QT syndrome, in Cardiac Electrophysiology: From Cell to Bedside (Zipes, D. P., and Jalife, J., ed.), W. B. Saunders, Philadelphia, PA, pp. 788–811.
Dumaine, R., Wang, Q., Keating, M. T., Hartmann, H. A., Schwartz, P. J., Brown, A. M., and Kirsch, G. E. (1996) Multiple mechanisms of Na+ channel-linked long-QT syndrome. Circ. Res. 78, 916–924.
Bennett, P. B., Yazawa, K., Makita, N., and George, A. L. (1995) Molecular mechanism for an inherited cardiac arrhythmia. Nature 376, 683–685.
Brugada, J. and Brugada, P. (1996) What to do in patients with no structural heart disease and sudden arrhythmic death? Am. J. Cardiol. 78, 69–75.
Aizawa, Y., Tamura, M., Chinushi, M., Naitoh, N., Uchiyama, H., Kusano, Y., Hosono, H., and Shibata, A. (1993) Idiopathic ventricular fibrillation and bradycardia-dependent intraventricular block. Am. Heart J. 126, 1473–1474.
Brugada, J., Brugada, R., and Brugada, P. (1997) Right bundle branch block and ST segment elevation in leads V1–V3: a marker for sudden death in patients without demonstrable structural heart diesease. Circ. 96, 1–151.
Brown, A. M., Lee, K. S., and Powell, T. (1981) Sodium current in single rat heart muscle cells. J. Phisiol. (London) 318, 479–500.
Makita, N., Sharai, N., Nagashima, M., Matsuoka, R., Yamada, Y., Tohse, N., and Kitabatake, A. (1998) A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome. FEBS Letters 423, 5–9.
Chen, Q., Kirsch, G. E., Zhang, D., Brugada, R., Brugada, J., Brugada, P., et al. (1998) Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 392, 293–296.
Rook, M. B., Alshinawi, C. B., Groenewegen, W. A., Gelder, I. C., Ginneken, A. C. G., Jongsma, H. J., et al. (1999) Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome. Cardiovasc. Res. 44, 507–517.
Attwell, D., Cohen, I., Eisner, D., Ohba, M., and Ojeda, C. (1979) The steady state TTX-sensitive (“window”) sodium current in cardiac purkinje fibers. Pflugers Arch. 379, 137–142.
Wang, D. W., Makita, N., Kitabatake, A., Balser, J. R., and George, A. L., Jr. (2000) Enhanced Na+ channel intermediate inactivation in Brugada syndrome. Circ. Res. 87, e37-e43.
Vilin, Y. Y., Fujimoto, E., and Ruben, P. C. (2001) A novel mechanism associated with idiopathic ventricular fibrillation (IVF) mutations R1232W and T1620M in human cardiac sodium channels. Pflugers Arch. 442, 204–211.
Rossie, S. and Catterall, W. A. (1987) Cyclic AMP-dependent phosphorylation of voltage-sensitive sodium channels in primary cultures of rat brain neurons. J. Biol. Chem. 262, 12,735–12,744.
Rossie, S., Gordon, D., and Catterall, W. A. (1987) Identification of an intracellular domain of the sodium channel having multiple cAMP-dependent phosphorylation sites. J. Biol. Chem. 262, 17,530–17,535.
Yang, J. and Barchi, R. (1990) Phosphorylation of the rat skeletal muscle sodium channel by cyclic AMP-dependent protein kinase. J. Neurochem. 54, 954–962.
Smith, R. D. and Goldin, A. L. (2000) Potentiation of rat brain sodium channel currents by PKA in Xenopus oocytes involves the I–II linker. Am. J. Physiol. 278, C638-C645.
Gershon, E., Weigl, L., Lotan, I., Schreibmayer, W., and Dascal, N. (1992) Protein kinase A reduces voltage-dependent Na+ current in Xenopus oocytes. J. Neurosci. 12, 3743–3752.
Numann, R., Hauschka, S. D., Catterall, W. A., and Scheuer, T. (1994) Modulation of skeletal muscle sodium channels in a statellite cell line by protein kinase C. J. Neurosci. 14, 4226–4236.
Li, M., West, J. W., Numann, R., Murphy, B. j., Scheuer, T., and Catterall, W. A. (1993) Convergent regulation of sodium channels by protein kinase C and cAMP-dependent protein kinase. Science 261, 1439–1442.
Murray, K. T., Hu, N., Daw, J. R., Shin, H. G., Watson, M. T., Mashburn, A. B., and George, A. L. (1997) Functional effects of protein kinase C activation on the human cardiac Na+ channel. Circ. Res. 80, 370–376.
Zhou, J., Yi, J., Hu, N. N., George, A. L., Jr., and Murray, K. T. (2000) Activation of protein kinase A modulates trafficking of the human cardiac sodium channel in Xenopus oocytes. Circ. Res. 87, 33–38.
Matsuda, J. J., Lee, H., and Shibata, E. F. (1992) Enhancement of rabbit cardiac sodium channels by β-adrenergic stimulation. Circ. Res. 70, 199–207.
Tomaselli, G. F., Marban, E., and Yellen, G. (1989) Sodium channels from human brain RNA expressed in Xenopus oocytes. Basic electrophysiologic characteristic and their modification by diphenylhudantoin. J. Clin. Invest. 83, 1724–1732.
Willow, M., Gonoi, T., and Catterall, W. A. (1985) Voltage clamp analysis of the inhibitory actions of diphenylhydantoin and carbamazepine on voltage-sensitive sodium channels in neuroblastoma cells. Mol. Pharmacol. 27, 549–558.
Stuart, G. J. and Sakmann, B. (1994) Active propagation of somatic action potentials into neocortical pyramidal cell dendrites. Nature 367, 69–72.
Williams, S. R. and Stuart, G. J. (1999) Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons. J. Physiol. (London) 521, 467–482.
Hausser, M., Stuart, G., Racca, C., and Sakmann, B. (1995) Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron 15, 637–647.
Simoncini, L. and Stuhmer, W. (1987) Slow sodium channel inactivation in rat fast-twitch muscle. J. Physiol. (London) 383, 327–337.
Ruff, R. L., Simoncini, L., and Stuhmer, W. (1987) Comparison between slow sodium channel inactivation in rat slow- and fast-twitch muscle. J. Physiol. (London) 383, 339–348.
Narahashi, T. (1964) Restoration of action potential by anodal polarization in lobster giant axons. J. Cell. Comp. Physiol. 64, 73–96.
Adelman, W. J. and Palti, Y. (1969) The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo peali, J. Gen. Physiol. 57, 745–758.
Schauf, C. L., Peneck, T. L., and Davis, F. A. (1976) Slow inactivation in Mixocola axons. Biophys. J. 16, 771–778.
Brismar, T. (1977) Slow mechanism for sodium permeability inactivation in myelinated nerve fiber of Xenopus laevis. J. Physiol. 270, 283–297.
Quandt, F. N. (1987) Burst kinetics of sodium channels which lack fast inactivation in mouse neuroblastoma cells. J. Physiol. 392, 563–585.
Hodgkin, A. L. and Huxley, A. F. (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. (London) 117, 500–544.
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Vilin, Y.Y., Ruben, P.C. Slow inactivation in voltage-gated sodium channels. Cell Biochem Biophys 35, 171–190 (2001). https://doi.org/10.1385/CBB:35:2:171
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DOI: https://doi.org/10.1385/CBB:35:2:171