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

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