The effects of intracellular Ca2+ on cardiac K+ channel expression and activity: Novel insights from genetically altered mice

Yanfang Xu, Zhao Zhang, Valeriy Timofeyev, Dipika Sharma, Danyan Xu, Dipika Tuteja, Pei Hong Dong, Gias Uddin Ahmmed, Yong Ji, Gary E. Shull, Muthu Periasamy, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

We tested the hypothesis that chronic changes in intracellular Ca2+ (Cai2+) can result in changes in ion channel expression; this represents a novel mechanism of crosstalk between changes in Ca2+ cycling proteins and the cardiac action potential (AP) profile. We used a transgenic mouse with cardiac-specific overexpression of sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoform 1a (SERCA1a OE) with a significant alteration of SERCA protein levels without cardiac hypertrophy or failure. Here, we report significant changes in the expression of a transient outward K+ current (Ito,f), a slowly inactivating K+ current (IK,slow) and the steady state current (ISS) in the transgenic mice with resultant prolongation in cardiac action potential duration (APD) compared with the wild-type littermates. In addition, there was a significant prolongation of the QT interval on surface electrocardiograms in SERCA1a OE mice. The electrophysiological changes, which correlated with changes in Cai2+, were further corroborated by measuring the levels of ion channel protein expression. To recapitulate the in vivo experiments, the effects of changes in Cai2+ on ion channel expression were further tested in cultured adult and neonatal mouse cardiac myocytes. We conclude that a primary defect in Ca2+ handling proteins without cardiac hypertrophy or failure may produce profound changes in K+ channel expression and activity as well as cardiac AP.

Original languageEnglish (US)
Pages (from-to)745-758
Number of pages14
JournalJournal of Physiology
Volume562
Issue number3
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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    Xu, Y., Zhang, Z., Timofeyev, V., Sharma, D., Xu, D., Tuteja, D., Dong, P. H., Ahmmed, G. U., Ji, Y., Shull, G. E., Periasamy, M., & Chiamvimonvat, N. (2005). The effects of intracellular Ca2+ on cardiac K+ channel expression and activity: Novel insights from genetically altered mice. Journal of Physiology, 562(3), 745-758. https://doi.org/10.1113/jphysiol.2004.076216