Enhancement of I_Ks potassium current in guinea-pig atrial myocytes by lysophosphatidic acid

Abstract

Lysophosphatidic acid (LPA) is a bioactive phospholipid that affects diverse cellular functions such as cell proliferation and differentiation. In recent years it has also been shown that many of these actions are mediated through the G protein-coupled plasma membrane receptors highly selective for LPA. There is, however, little information concerning the acute electrophysiological effects of LPA on ion channel functions in the heart. The present study was designed to examine the effect of LPA on the slow component of delayed rectifier K⁺ current (I_Ks) in guinea-pig atrial myocytes using the whole-cell patch-clamp method. Extracellular application of LPA reversibly increased I_Ks, elicited by 2-s depolarizing voltage pulses to various levels (up to +50 mV) applied from a holding potential of -50 mV. The stimulatory effect was concentration-dependent with mean half-maximal concentration (K_1/2) of 3.9 nM, and the maximal effect (increase by 107.4±15.2%, n = 14) was obtained by 1 μM LPA. The LPA-induced enhancement of I_Ks was markedly attenuated by intracellular loading with nonhydrolyzable GDP analogue GDPβS (2 mM) but was not significantly affected by pretreatment with pertussis toxin (PTX, 5 mg/ml). These results strongly suggest that the stimulatory effect of LPC is mediated through the plasma membrane receptor coupled to a PTX-insensitive G protein. The present observation that I_Ks receives a positive regulation by LPA indicates that LPA can produce acute action on the repolarizing process in cardiac myocardium. [Jpn J Physiol 54 Suppl:S126 (2004)]