Involvement of lipid rafts and caveolae in cardiac ion channel function

Abstract

A variety of lipid microdomains, including caveolae, have been shown to play an important role in both protein targetting and in controlling protein-protein interactions. There is increasing evidence for significant ion channel localization in lipid rafts. Cardiac channel subunits known to localize in lipid rafts include Kv1.4, Kv1.5, Kv2.1, Kv4, Kir2, Kir3, K(ATP), Nav and Cav subunits. This article reviews what is known about the occurrence and functional significance of cardiac ion channel/lipid raft interactions. Much remains to be learned about this area of potentially enormous importance to cardiac function in health and disease.

α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac KV4 channels

“…26,27 In our electron micrographs the K V 4.3 channel is always located at the neck of the caveolae, avoiding this hypothetical shortcoming. Recent studies employing electron microscopy reveal that insulin receptors also associate predominantly with the neck, but not the bulb, of caveolae.…”

Identification of Novel Cholesterol-binding Regions in Kir2 Channels

“…As hinted by its name, the CARC motif, (R/K)X [1][2][3][4][5] Our data show that there is a partial overlap between the first CARC motif and the cholesterol-binding region that we have identified at the interface of the TM domain with the cytosolic domain (putative cholesterol-binding region 2). Specifically, as we have shown in Fig.…”

“…An increase in membrane cholesterol has been shown to regulate different types of K ϩ channels, Ca 2ϩ channels, Na ϩ channels, and Cl Ϫ channels, as described in detail in several recent reviews (1)(2)(3)(4). The most common effect of cholesterol on ion channels is a decrease in channel activity that may be due to a decrease in the open probability, in the unitary conductance, and/or in the number of active channels in the membrane.…”

Multiple functions of ergosterol in the fission yeast Schizosaccharomyces pombe

“…This membrane microdomain is called the lipid raft, which corresponds to a related structure, the caveola, in mammalian membranes. Many functions have been attributed to these structures, including cholesterol transport, endocytosis and signal transduction (Alonso & Millán, 2001;Pelkmans, 2005;Maguy et al, 2006;Wachtler & Balasubramanian, 2006). The most widely used assay for rafts is based on the observation that a subset of associated plasma membrane components is resistant to nonionic detergents, such as Triton X-100, at 4 u C (Bagnat et al, 2000).…”