Depression of excitability by sphingosine 1-phosphate in rat ventricular myocytes

Sphingosine 1-phosphate (S-1-P) is a bioactive sphingolipid that is release d from activated platelets. Extracellular S-1-P augments an inwardly rectif ying potassium conductance in cultured atrial preparations, but the electro physiological effects of this compound in the ventricle are unknown. The el ectrophysiological effects of S-1-P were examined in single myocytes from r at ventricular muscle. Action potential waveforms and underlying ionic curr ents in the presence and absence of 3 mu M S-1-P (1-6 min) were recorded. S -1-P increased the minimum stimulus current needed to elicit an action pote ntial by similar to 100 pA. Pertussis toxin or preexposure to S-1-P did not alter this effect. The action potential waveform was unchanged by S-1-P. T he inward sodium current (I-Na) was examined in a range of membrane potenti als just negative to the potential for firing an action potential. S-1-P re versibly inhibited peak I-Na by similar to 50 pA, whereas the inward rectif ier potassium current was not significantly changed. The results of this st udy suggest that S-1-P inhibits rat ventricular excitability by reducing I- Na.