抄録
In recent years, some of biological actions of lysophosphotidylcholine (LPC) have been found to be mediated through a class of G protein-coupled receptors, termed G2A. The present study was designed to examine the possible regulation of the muscarinic K+ current (IK,ACh) by LPC and its associated signaling pathways in guinea-pig atrial myocytes, using whole-cell patch-clamp method. Bath application of LPC (2 μM) reversibly and almost completely (93.3%; n = 9) inhibited IK,ACh preactivated by acetylcholine (ACh). On the other hand, LPC almost irreversibly inhibited IK,ACh preactivated by intracellular loading of non-hydrolyzable GTP analogue GTPγS (84.2%; n = 6), suggesting an involvement of G protein. The inhibitory action of LPC was partially, but significantly, attenuated by pretreating myocytes with an anti-G2A antibody and phospholipase C (PLC) blockers (compound 48/80 and neomycin). Furthermore, the inhibitory effect of LPC was still significantly reduced by exogenously adding phosphatidylinositol 4,5-bisphosphate (PIP2, 50 μM) to the cell inside, and became nearly irreversible when atrial myocytes were continuously exposed to wortmannin (10 μM), which suppresses the resynthesis of PIP2. As expected, LPC greatly reversed the shortening of action potential duration evoked by ACh. Based on these results, we conclude that LPC markedly inhibits IK,ACh through a mechanism involving an activation of G protein-coupled G2A receptor causing a depletion of membrane PIP2 via PLC activation. [J Physiol Sci. 2006;56 Suppl:S128]
