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Functional expression and properties of the human skeletal muscle sodium channel

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Abstract

Full-length deoxyribonucleic acid, complementary (cDNA) constructs encoding theα-subunit of the adult human skeletal muscle Na+ channel, hSkM1, were prepared. Functional expression was studied by electrophysiological recordings from cRNA-injectedXenopus oocytes and from transiently transfected tsA201 cells. The Na+ currents of hSkM1 had abnormally slow inactivation kinetics in oocytes, but relatively normal kinetics when expressed in the mammalian cell line. The inactivation kinetics of Na+ currents in oocytes, during a depolarization, were fitted by a weighted sum of two decaying exponentials. The time constant of the fast component was comparable to that of the single component observed in mammalian cells. The block of hSkM1 Na+ currents by the extracellular toxins tetrodotoxin (TTX) and μ-conotoxin (μCTX) was measured. The IC50 values were 25 nM (TTX) and 1.2 μM (μCTX) in oocytes. The potency of TTX is similar to that observed for the rat homolog rSkM1, but the potency of μCTX is 22-fold lower in hSkM1, primarily due to a higher rate of toxin dissociation in hSkM1. Single-channel recordings were obtained from outside-out patches of oocytes expressing hSkM1. The single-channel conductance, 24.9 pS, is similar to that observed for rSkM1 expressed in oocytes.

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Author notes

  1. Mohamed Chahine

    Present address: Centre de Recherche, Hôpital Laval, 2725 Chemin Sainte-Foy, GIV 4G5, Sainte-Foy, Québec, Canada

Authors and Affiliations

  1. Department of Physiology, Jefferson Medical College, 1020 Locust Street, 19107, Philadelphia, PA, USA

    Mohamed Chahine & Richard Horn

  2. Department of Medicine, S-3223 MCN, Vanderbilt University School of Medicine, 21st Street and Grand Avenue, 37232, Nashville, TN, USA

    Paul B. Bennett & Alfred L. George Jr

  3. Department of Pharmacology, S-3223 MCN, Vanderbilt University School of Medicine, 21st Street and Grand Avenue, 37232, Nashville, TN, USA

    Paul B. Bennett & Alfred L. George Jr

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  1. Mohamed Chahine
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  3. Alfred L. George Jr
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  4. Richard Horn
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Chahine, M., Bennett, P.B., George, A.L. et al. Functional expression and properties of the human skeletal muscle sodium channel. Pflügers Arch. 427, 136–142 (1994). https://doi.org/10.1007/BF00585952

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  • DOI: https://doi.org/10.1007/BF00585952

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