Lysophosphatidylcholine increases Ca2+ current via activation of protein kinase C in rabbit portal vein smooth muscle cells

Lysophosphatidylcholine (LPC), a metabolite of membrane phospholipids by phospholipase A(2), has been considered responsible for the development of abnormal vascular reactivity during atherosclerosis. Ca2+ influx was shown to be augmented in atherosclerotic artery which might be responsible for abnormal vascular reactivity. However, the mechanism underlying Ca2+ influx change in atherosclerotic artery remains undetermined. The purpose of the present study was to examine the effects of LPC on L-type Ca2+ current (I-Ca(L)) activity and to elucidate the mechanism of LPC-induced change of I-Ca(L) in rabbit portal vein smooth muscle cells using whole cell patch clamp. Extracellular application of LPC increased I-Ca(L) through whole test potentials, and this effect was readily reversed by washout. Steady state voltage dependency of activation or inactivation properties of I-Ca(L) was not significantly changed by LPC. Staurosporine (100 nM) or chelerythrine (3 mu M), which is a potent inhibitor of PKC, significantly decreased basal I-Ca(L), and LPC-induced increase of I-Ca(L) was significantly suppressed in the presence of PKC inhibitors. On the other hand, application of PMA, an activator of PKC, increased basal I-Ca(L) significantly, and LPC-induced enhancement of I-Ca(L) was abolished by pretreatment of the cells with PMA. These findings suggest that LPC increased I-Ca(L) in vascular smooth muscle cells by a pathway that involves PKC, and that LPC-induced increase of I-Ca(L) might be, at least in part, responsible for increased Ca2+ influx in atherosclerotic artery.