Isoform-specific modulation of voltage-gated Na(+) channels by calmodulin.

Isabelle Deschênes, Nathalie Neyroud, Deborah DiSilvestre, Eduardo Marbán, David T. Yue, Gordon F. Tomaselli

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Calmodulin (CaM) is a calcium-sensing protein that binds to Na(+) channels, with unknown functional consequences. Wild-type CaM produced a hyperpolarizing shift in the steady-state availability of expressed skeletal muscle (micro1) but not cardiac (hH1) Na(+) channels. Mutant CaM(1234) did not alter the voltage dependence or the kinetics of gating of either micro1 or hH1. Mutation of the highly conserved IQ motif in the carboxyl terminus of both isoforms (IQ/AA) slowed the kinetics of current decay and abolished the effect of wild-type CaM on micro1, but did not alter hH1 currents. The IQ/AA mutation eliminated CaM binding to the carboxyl terminus of both micro1 and hH1 channels. Inhibition of Ca(2+)/CaM kinase (CaM-K) slowed the current decay, the rate of entry into inactivation, and shifted the voltage dependence of hH1 in the depolarizing direction independent of CaM overexpression with no effect on micro1 Na(+) channels. CaM signaling modulates Na(+) currents in an isoform-specific manner, via direct interaction with skeletal muscle Na(+) channels and through CaM-K in the case of the cardiac isoform. The full text of this article is available at http://www.circresaha.org.

Original languageEnglish (US)
JournalCirculation Research
Volume90
Issue number4
StatePublished - Mar 8 2002
Externally publishedYes

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Calmodulin
Protein Isoforms
Skeletal Muscle
Calcium-Calmodulin-Dependent Protein Kinases
Mutation
Calcium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Deschênes, I., Neyroud, N., DiSilvestre, D., Marbán, E., Yue, D. T., & Tomaselli, G. F. (2002). Isoform-specific modulation of voltage-gated Na(+) channels by calmodulin. Circulation Research, 90(4).

Isoform-specific modulation of voltage-gated Na(+) channels by calmodulin. / Deschênes, Isabelle; Neyroud, Nathalie; DiSilvestre, Deborah; Marbán, Eduardo; Yue, David T.; Tomaselli, Gordon F.

In: Circulation Research, Vol. 90, No. 4, 08.03.2002.

Research output: Contribution to journalArticle

Deschênes, I, Neyroud, N, DiSilvestre, D, Marbán, E, Yue, DT & Tomaselli, GF 2002, 'Isoform-specific modulation of voltage-gated Na(+) channels by calmodulin.', Circulation Research, vol. 90, no. 4.
Deschênes I, Neyroud N, DiSilvestre D, Marbán E, Yue DT, Tomaselli GF. Isoform-specific modulation of voltage-gated Na(+) channels by calmodulin. Circulation Research. 2002 Mar 8;90(4).
Deschênes, Isabelle ; Neyroud, Nathalie ; DiSilvestre, Deborah ; Marbán, Eduardo ; Yue, David T. ; Tomaselli, Gordon F. / Isoform-specific modulation of voltage-gated Na(+) channels by calmodulin. In: Circulation Research. 2002 ; Vol. 90, No. 4.
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