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

121 Citations (Scopus)

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

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Hyperkalemic Periodic Paralysis
Mutation
Muscles
Inborn Genetic Diseases
Pedigree
Base Pairing
Skeletal Muscle
Complementary DNA
Kidney

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis. / Cummins, Theodore R.; Zhou, Jiuying; Sigworth, Frederick J.; Ukomadu, Chinwe; Stephan, Megan; Ptáčk, Louis J.; Agnew, William S.

In: Neuron, Vol. 10, No. 4, 04.1993, p. 667-678.

Research output: Contribution to journalArticle

Cummins, TR, Zhou, J, Sigworth, FJ, Ukomadu, C, Stephan, M, Ptáčk, LJ & Agnew, WS 1993, 'Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis', Neuron, vol. 10, no. 4, pp. 667-678. https://doi.org/10.1016/0896-6273(93)90168-Q
Cummins, Theodore R. ; Zhou, Jiuying ; Sigworth, Frederick J. ; Ukomadu, Chinwe ; Stephan, Megan ; Ptáčk, Louis J. ; Agnew, William S. / Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis. In: Neuron. 1993 ; Vol. 10, No. 4. pp. 667-678.
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