Cold-induced defects of sodium channel gating in atypical periodic paralysis plus myotonia.

Jadon Webb, Stephen C. Cannon

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

BACKGROUND: Missense mutations of the skeletal muscle voltage-gated sodium channel (NaV1.4) are an established cause of several clinically distinct forms of periodic paralysis and myotonia. The mechanistic basis for the phenotypic variability of these allelic disorders of muscle excitability remains unknown. An atypical phenotype with cold-induced hypokalemic paralysis and myotonia at warm temperatures was reported to segregate with the P1158S mutation. OBJECTIVE: This study extends the functional characterization of the P1158S mutation and tests the specific hypothesis that impairment of Na channel slow inactivation is a common feature of periodic paralysis. METHODS: Mutant NaV1.4 channels (P1158S) were transiently expressed in human embryonic kidney cells and characterized by voltage-clamp studies of Na currents. RESULTS: Wild-type and P1158S channels displayed comparable behavior at 37 degrees C, but upon cooling to 25 degrees C, mutant channels activated at more negative potentials and slow inactivation was destabilized. CONCLUSIONS: Consistent with other NaV1.4 mutations associated with a paralytic phenotype, the P1158S mutation disrupts slow inactivation. The unique temperature sensitivity of the channel defect may contribute to the unusual clinical phenotype.

Original languageEnglish (US)
Pages (from-to)755-761
Number of pages7
JournalNeurology
Volume70
Issue number10
DOIs
StatePublished - Mar 4 2008

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Myotonia
Sodium Channels
Paralysis
Mutation
Phenotype
NAV1.4 Voltage-Gated Sodium Channel
Temperature
Muscular Diseases
Missense Mutation
Skeletal Muscle
Kidney

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cold-induced defects of sodium channel gating in atypical periodic paralysis plus myotonia. / Webb, Jadon; Cannon, Stephen C.

In: Neurology, Vol. 70, No. 10, 04.03.2008, p. 755-761.

Research output: Contribution to journalArticle

Webb, Jadon ; Cannon, Stephen C. / Cold-induced defects of sodium channel gating in atypical periodic paralysis plus myotonia. In: Neurology. 2008 ; Vol. 70, No. 10. pp. 755-761.
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