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 (ICa(L)) activity and to elucidate the mechanism of LPC-induced change of ICa(L) in rabbit portal vein smooth muscle cells using whole cell patch clamp. Extracellular application of LPC increased ICa(L) through whole test potentials, and this effect was readily reversed by washout. Steady state voltage dependency of activation or inactivation properties of ICa(L) was not significantly changed by LPC. Staurosporine (100 nanometer) or chelerythrine (3 micrometer, which is a potent inhibitor of PKC, significantly decreased basal ICa(L), and LPC-induced increase of ICa(L) was significantly suppressed in the presence of PKC inhibitors. On the other hand, application of PMA, an activator of PKC, increased basal ICa(L) significantly, and LPC-induced enhancement of ICa(L) was abolished by pretreatment of the cells with PMA. These findings suggest that LPC increased ICa(L) in vascular smooth muscle cells by a pathway that involves PKC, and that LPC-induced increase of ICa(L) might be, at least in part, responsible for increased Ca2+ influx in atherosclerotic artery.
Arteries ; Atherosclerosis ; Benzophenanthridines ; Dependency (Psychology) ; Hand ; Lysophosphatidylcholines ; Membranes ; Muscle, Smooth ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Phospholipases ; Phospholipids ; Portal Vein ; Protein Kinase C ; Protein Kinases ; Staurosporine