Caveolae and arrhythmogenesis

Abstract

Caveolae are flask-shaped invaginations of the plasma membrane measuring approximately 50-100 nm in diameter. Caveolae are particularly rich in cholesterol and glycosphingolipids, and they are involved in a wide variety of biological processes such as membrane endocytosis, cholesterol homeostasis, tumorigenesis and cellular signaling. In the last several years, these microdomains, greatly abundant in the cardiovascular system and in particular the myocardium, were investigated for their capacity to concentrate and compartmentalize various signaling molecules such as adrenergic receptors, which have been also involved in the modulation of ion channels function. In addition, various ion channels were identi fied have been found to clustered to caveolae or been physically linked to caveolins, the major determinants of caveolae. Nevertheless, the relationship between the metabolism of caveolae and the ion channels function remains poorly understood. However, recent advances in the molecular genetics of caveolins revealed a tight connection between these microdomains and the susceptibility to arrhythmogenesis in humans suggesting an increasingly important role of these plasmalemmal organelles in traf ficking and regulation of ion channel function.