Characterization of Ca2+ channels involved in endothelin-1-induced mitogenic responses in vascular smooth muscle cells

Ca2+ channels involved in the endothelin-l-induced mitogenic response of cultured rat thoracic aorta smooth muscle cells, A7r5 cells, were characterized using the Ca2+ channel blockers, LOE 908 and SK&F 96365. Stimulation of A7r5 cells with endothelin-1 induced a mitogenic response as well as a biphasic increase in the intracellular-free Ca2+ concentration. Based on the sensitivity to nifedipine, a specific blocker of L-type voltage-operated Ca2+ channel (VOCC), Ca2+ influx through VOCC has a minor role in endothelin-1-induced mitogenic responses. On the other hand. Ca2+ influx through voltage-independent Ca2+ channels (VICCs) plays an important part in endothelin-1-induced mitogenesis. Moreover based on their sensitivity to SK&F 96365 and LOE 908, VICCs consist of two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC). Ca2+ influx through NSCC-1, NSCC-2 and SOCC contributes to 35%, 30% and 35%, respectively, to the nifedipine-resistant component of the endothelin-1 mitogenic response. (C) 2001 Published by Elsevier Science B.V.