POTENTIATION OF IKS POTASSIUM CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES BY SPHINGOSINE-1-PHOSPHATE

摘要

Sphingosine-1 -phosphate (SIP) elicits a diversity of cellular responses by binding to G-protein-coupled endothelial differentiation gene-encoded (Edg) receptors. The present study was undertaken to examine the effect of SIP on the slowly activating component of delayed rectifier K+ current (I_(Ks)) in guinea-pig ventricular myocytes using the whole-cell patch-clamp technique. I_(Ks) was elicited by depolarizing voltage steps given from a holding potential of -50 mV to various levels up to +50 mV and the effect of SIP on I_(Ks) was assessed by measuring the amplitude of the tail current elicited upon return to the holding potential. External application of S IP reversibly increased the amplitude of I_(Ks) in a concentration-dependent manner with a half-maximal concentration (K_(1/2)) of 69.7 nM (n = 6). SIP at 1 MuM maximally increased I_(Ks) by a factor of 1.68+-0.1 (n = 6). SIP did not appreciably affect the current kinetics of I_(Ks). Preincubation of ventricular myocytes with pertussis toxin (PTX, 5 Mug/mL) largely abolished the stimulatory action of SIP, suggesting that SIP action is mediated through a PTX-sensitive G protein. Thus the present investigation identifies a novel extracellular signalling molecule that stimulates I_(Ks) in mammalian ventricular myocytes.