Control of cardiac Ca2+ levels: Inhibitory actions of sphingosine on Ca2+ transients and L-type Ca2+ channel conductance. Circ. Res

Abstract The naturally occurring second messenger sphin-gosine (SPH) was examined for its ability to influence cardiac myocyte Ca2 ' regulation. SPH inhibited intracellular Ca'+ transients in adult and neonatal rat ventricular myocytes. The inhibition was steeply dose dependent, with complete blockage of the Ca'+ transients occurring in the 20- to 25-,umol/L range. Whole-cell patch clamping revealed substantial inhibition of the L-type Ca2 channel current (lCa) by SPH. The ability of SPH to block both the Ca21 transients and Ic was not dependent on protein kinases, since the general protein kinase inhibitor H7 failed to prevent the actions of SPH. The specificity of the effect of SPH was determined in experiments showing that SPH analogues did not produce comparable effects. Neither the naturally occurring ceramide, N-stearoyl SPH, nor the cell-permeant ceramide, N-acetyl SPH, ha