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

Sphingosine 1-phosphate (S-1-P) is a bioactive sphingolipid that is released from activated platelets. Extracellular S-1-P augments an inwardly rectifying potassium conductance in cultured atrial preparations, but the electrophysiological effects of this compound in the ventricle are unknown. The electrophysiological effects of S-1-P were examined in single myocytes from rat ventricular muscle. Action potential waveforms and underlying ionic currents in the presence and absence of 3 microM S-1-P (1-6 min) were recorded. S-1-P increased the minimum stimulus current needed to elicit an action potential by approximately 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. The inward sodium current (INa) was examined in a range of membrane potentials just negative to the potential for firing an action potential. S-1-P reversibly inhibited peak INa by approximately 50 pA, whereas the inward rectifier potassium current was not significantly changed. The results of this study suggest that S-1-P inhibits rat ventricular excitability by reducing INa.