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Prog Biophys Mol Biol. 2008 Oct-Nov;98(2-3):149-60. doi: 10.1016/j.pbiomolbio.2009.01.012. Epub 2009 Jan 30.

Caveolae, ion channels and cardiac arrhythmias.

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  • 1Department of Medicine, Cellular and Molecular Arrhythmia Research Program, University of Wisconsin, Madison, WI 53792, USA.

Abstract

Caveolae are specialized membrane microdomains enriched in cholesterol and sphingolipids which are present in multiple cell types including cardiomyocytes. Along with the essential scaffolding protein caveolin-3, a number of different ion channels and transporters have been localized to caveolae in cardiac myocytes including L-type Ca2+ channels (Ca(v)1.2), Na+ channels (Na(v)1.5), pacemaker channels (HCN4), Na+/Ca2+ exchanger (NCX1) and others. Closely associated with these channels are specific macromolecular signaling complexes that provide highly localized regulation of the channels. Mutations in the caveolin-3 gene (CAV3) have been linked with the congenital long QT syndrome (LQT9), and mutations in caveolar-localized ion channels may contribute to other inherited arrhythmias. Changes in the caveolar microdomain in acquired heart disease may also lead to dysregulation and dysfunction of ion channels, altering the risk of arrhythmias in conditions such as heart failure. This review highlights the existing evidence identifying and characterizing ion channels localized to caveolae in cardiomyocytes and their role in arrhythmogenesis.

PMID:
19351512
[PubMed - indexed for MEDLINE]
PMCID:
PMC2836876
Free PMC Article

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