Impaired slow inactivation in mutant sodium channels

Theodore Cummins, Frederick J. Sigworth

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Hyperkalemic periodic paralysis (HyperPP) is a disorder in which current through Na+ channels causes a prolonged depolarization of skeletal muscle fibers, resulting in membrane inexcitability and muscle paralysis. Although HyperPP mutations can enhance persistent sodium currents, unaltered slow inactivation would effectively eliminate any sustained currents through the mutant channels. We now report that rat skeletal muscle channels containing the mutation T698M, which corresponds to the human T704M HyperPP mutation, recover very quickly from prolonged depolarizations. Even after holding at - 20 mV for 20 min, ~25% of the maximal sodium current is available subsequent to a 10-ms hyperpolarization (-100 mV). Under the same conditions, recovery is less than 3% in wild-type channels and in the F1304Q mutant, which has impaired fast inactivation. This effect of the T698M mutation on slow inactivation, in combination with its effects on activation, is expected to result in persistent currents such as that seen in HyperPP muscle.

Original languageEnglish (US)
Pages (from-to)227-236
Number of pages10
JournalBiophysical Journal
Volume71
Issue number1
StatePublished - Jul 1996
Externally publishedYes

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Hyperkalemic Periodic Paralysis
Sodium Channels
Mutation
Sodium
Muscles
Skeletal Muscle Fibers
Paralysis
Skeletal Muscle
Membranes

ASJC Scopus subject areas

  • Biophysics

Cite this

Impaired slow inactivation in mutant sodium channels. / Cummins, Theodore; Sigworth, Frederick J.

In: Biophysical Journal, Vol. 71, No. 1, 07.1996, p. 227-236.

Research output: Contribution to journalArticle

Cummins, T & Sigworth, FJ 1996, 'Impaired slow inactivation in mutant sodium channels', Biophysical Journal, vol. 71, no. 1, pp. 227-236.
Cummins, Theodore ; Sigworth, Frederick J. / Impaired slow inactivation in mutant sodium channels. In: Biophysical Journal. 1996 ; Vol. 71, No. 1. pp. 227-236.
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