Modulation of Ca by agents affecting voltage-sensitive Ca channels in mesangial cells

The purpose of this study was to investigate the effects of depolarizing media and of Ca-channel activators and blockers on cytosolic free Ca in cultured rat mesangial cells. Membrane depolarizing media, containing 10-100 mM K+, dose dependently increased cytosolic Ca, and this effect was sustained and reversible. Nifedipine and lanthanum ion inhibited this increase, whereas verapamil was ineffective. A Ca-channel activator, BAY K 8644, dose dependently increased resting Ca levels, and nifedipine inhibited this effect. Moreover, the increase of Ca induced by maximally effective high K+ and BAY K 8644 was additive, suggesting differential mechanisms of action for the two channel activators. Nifedipine and verapamil decreased resting Ca levels by up to 35-40%. The results support the idea that mesangial cells have spontaneously active Ca channels that can be further activated by membrane depolarization or by the Ca-channel activator, BAY K 8644, and inhibited by the Ca-channel blockers, nifedipine or verapamil. Voltage-sensitive Ca channels in mesangial cells may play a role in the regulation of the glomerular filtration rate.