抄録
We examined with a lipid bilayer method how the single channel currents of cardiac RyR channels are modified by pathophysiological metabolites from the sarcolemmmal membrane phospholipids. During the apoptosis and the hyperlipidemia, sphingosylphosphatidylcholine (SPC) is metabolized from sphingomyelin (SM) of a minor sarcolemmal phospholipid. (1-1) The cytoplasmic-side addition of SPC blocked the RyR channels at the μM level, while the SR luminal-side addition of SPC did not affect. (1-2) SPC unaltered the membrane capacitance. Thus, SPC could exert a specific effect via an intermolecular binding to the cytoplasmic domain of the RyR molecule, although SPC belongs to the lipid. Kinetics of a long-lived blocking state of the SPC-modified channels is characterized by an extremely low dissociation rate constant. During the cardiac ischemia, lysophosphatidylcholine (LPC) is produced from phosphatidylcholine (PC) of a major sarcolemmal phospholipid. (2-1) Both cytoplasmic-side and SR luminal-side additions of LPC activated the RyR channels at the μM level. (2-2) LPC increased the membrane capacitance. In contrast to SPC effects, LPC could thus exert an indirect effect via a fusion of LPC into the membrane lipids on the RyR channel. Here we propose that a second messenger metabolited from SM of sarcolemmmal membrane phospholipids specifically regulated in vivo cardiac RyR channel activities. [J Physiol Sci. 2006;56 Suppl:S155]
