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

Thenaturally occurring second messenger sphin- gosine (SPH) wasexamined forits ability toinfluence cardiac myocyte Ca2'regulation. SPH inhibited intracellular Ca'+ transients inadult andneonatal ratventricular myocytes. The inhibition wassteeply dosedependent, with complete blockage oftheCa'+ transients occurring inthe20-to25-,umol/L range. Whole-cell patch clamping revealed substantial inhibition of theL-type Ca2 channel current (lCa) bySPH.Theability of SPH toblockboththeCa21transients andIcwasnot dependent onprotein kinases, since thegeneral protein kinase inhibitor H7 failed toprevent theactions ofSPH.The specificity oftheeffect ofSPHwasdetermined inexperiments showing thatSPH analogues didnotproduce comparable effects. Neither thenaturally occurring ceramide, N-stearoyl SPH,northecell-permeant ceramide, N-acetyl SPH,had