Effect of sphingosylphosphorylcholine on the single channel gating properties of the cardiac ryanodine receptor

The effects of the lysosphingolipid, sphingosylphosphorycholine (SPC), on the cardiac ryanodine receptor (RyR) were examined. The open probability of cardiac RyR incorporated in lipid bilayers was decreased by cytoplasmic, but not lumenal side application of micromolar concentrations of SPC, Modification of channel function was characterized by the appearance of a long-lived closed state in addition to the brief channel closings observed in the presence and absence of SPC, Open channel kinetics and ion conduction properties, however, were not altered by this compound. These results suggest that SPC, a putative second messenger derived from sphingomyelin, may regulate Ca2+ release from the sarcoplasmic reticulum by modifying the gating kinetics of the RyR. (C) 1999 Federation of European Biochemical Societies.