Cholesterol-saturated MβCD is efficient as cholesterol donor.

MβCD is quite specific for cholesterol, allowing enrichment or a relatively rapid sequestration of cholesterol from living cells. The β-cyclodextrins (seven glucose units) have high affinity for encapsulating cholesterol ( Ohtani et al., 1989). However, cholesterol is located in both rafts and non-raft fractions.Īn efficient method to modulate the content of plasma membrane cholesterol is by methyl-β-cyclodextrin (MβCD), which is a cyclic oligosaccharide ( Ohtani et al., 1989 Davis and Brewster, 2004). Plasma membrane cholesterol includes domains known as lipid rafts ( Pike, 2006). Accordingly, lipid raft perturbation by cholesterol sequestration could give clues to the function of lipid environment in TRPC channel activity and its mechanism.Ĭholesterol molecules are intercalated among the phospholipids of cell membrane forming an integral part of the plasma membrane, which is essential for the proper function of ion channels. It was thus suggested that the fast kinetics of TRPL channel suppression by MβCD arise from disruption of lipid rafts. When the Drosophila TRPL channel was expressed in S2 or HEK293 cells and perfused with MβCD, the TRPL current was abolished in less than 100 s, fitting well the fast kinetic phase of cholesterol sequestration experiments in cells. The Drosophila TRP and TRP-like (TRPL) channels belong to the TRPC channel subfamily. This perturbation was also shown to disrupt multimolecular signaling complexes containing TRPC channels. Thus, the observed inhibition of TRPC channels by methyl-β-cyclodextrin (MβCD), which induces cholesterol efflux from the plasma membrane, may result from disruption of lipid rafts. These perturbations have been shown to induce reversible targeting of mammalian transient receptor potential C (TRPC) channels to the cholesterol-rich membrane environment of lipid rafts.

The proposed mechanisms underlying these modulations include association of cholesterol to a single binding site at a single channel conformation, association to a highly flexible cholesterol binding site adopting multiple poses, and perturbation of lipid rafts. 2Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, United StatesĬhanges of cholesterol level in the plasma membrane of cells have been shown to modulate ion channel function.1Institute for Medical Research Israel-Canada (IMRIC), Edmond and Lily Safra Center for Brain Sciences (ELSC), Faculty of Medicine, The Hebrew University, Jerusalem, Israel.Barbera 2, Irena Levitan 2 and Baruch Minke 1* Rita Gutorov 1, Maximilian Peters 1, Ben Katz 1, Tal Brandwine 1, Nicolas A.

Raft People by M.L. Katz