Differential effects of Ca2+ channel blockers on Ca2+ transients and cell cycle progression in vascular smooth muscle cells

We examined the differential effects of Ca2+ channel blockers on the elevation of the cytosolic Ca2+ concentration ([Ca2+](i)) and G(0)/G(1) transition induced by platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells in primary culture. The phase of the cell cycle was determined by an immunocytochemical analysis of cell cycle-specific nuclear antigens. [Ca2+](i) was monitored bu fura-3-microfluorometry. The efficacy of Ca2+ channel blockers for the inhibition of [Ca2+](i) elevation induced by PDGF (NiCl2 > isradipine > verapamil = diltiazem) did not parallel that for the inhibition of cell cycle progression induced by PDGF (verapamil = diltiazem > NiCl2 > isradipine). In addition, no significant correlation was observed between the extent of [Ca2+](i) elevation and the extent of G(0)/G(1) transition. We thus conclude that the inhibitory effects of Ca2+ channel blockers on the G(0)/G(1) transition induced by PDGF are not simply due to their inhibitory action on the [Ca2+](i) elevations but instead are due to more complex unknown factors. (C) 1998 Elsevier Science B.V.