Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis

Theodore R. Cummins, Jiuying Zhou, Frederick J. Sigworth, Chinwe Ukomadu, Megan Stephan, Louis J. Ptáčk, William S. Agnew

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Hyperkalemic periodic paralysis (HYPP), one of several inheritable myotonic diseases, results from genetic defects in the human skeletal muscle Na+ channel. In some pedigrees, HYPP is correlated with a single base pair substitution resulting in a Met replacing Thr704 in the fifth transmembrane segment of the second domain. This region is totally conserved between the human and rat channels. We have introduced the human mutation into the corresponding region of the rat muscle Na+ channel cDNA and expressed it in human embryonic kidney 293 cells. Patch-clamp recordings show that this mutation shifts the voltage dependence of activation by 10-15 mV in the negative direction. The shift results in a persistent Na+ current that activates near -70 mV; this phenomenon could underlie the abnormal muscle activity observed in patients with HYPP.

Original languageEnglish (US)
Pages (from-to)667-678
Number of pages12
JournalNeuron
Volume10
Issue number4
DOIs
StatePublished - Apr 1993
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Cummins, T. R., Zhou, J., Sigworth, F. J., Ukomadu, C., Stephan, M., Ptáčk, L. J., & Agnew, W. S. (1993). Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis. Neuron, 10(4), 667-678. https://doi.org/10.1016/0896-6273(93)90168-Q