抄録
LPC has diverse actions on the function of various cell types including cardiac myocytes. Some of LPC actions are mediated through a G protein-coupled receptor highly selective for this phospholipid. The present study was designed to examine whether LPC receptor stimulation affects the slow component of delayed rectifier K+ current (IKs) in guinea-pig cardiac mycocytes and the KCNQ1/KCNE1 channel current heterologously expressed in HEK 293T cells, using the whole-cell patch-clamp method. Bath application of LPC (C16:0) concentration-dependently (EC50 = 1.1 μM) and reversibly increased IKs in atrial myocytes but produced minimal if any effect in ventricular myocytes. LPC (C6:0), LPC (C18:1) and phosphatidylcholine had almost no stimulatory effect on IKs. Pretreatment of atrial myocytes with an antibody against N-terminus of the LPC receptor G2A significantly reduced the LPC (C16:0)-induced potentiation of IKs. Immunohistochemistry confirmed that G2A-positive reaction was densely present in the plasma membrane of atrial myocytes but was much less distributed in that of ventricular myocytes. Blockers for heterotrimeric G proteins, phospholipase C (PLC) and protein kinase C (PKC) significantly attenuated the LPC (C16:0)-induced enhancement of IKs. LPC (C16:0) also significantly enhanced the KCNQ1/KCNE1 current when coexpressed with G2A but had little effect without coexpression of G2A. Thus, the present study provides strong evidence to suggest that stimulation of the G2A receptor coupled to G protein potentiates IKs via a PLC-PKC pathway. [Jpn J Physiol 55 Suppl:S129 (2005)]
