Calcium mobilization by cadmium or decreasing extracellular Na + or pH in coronary endothelial cells

Abstract

Replacing extracellular Na + with choline transiently increased cytoplasmic free Ca 2+ ([Ca 2+] i) more than 5-fold in coronary endothelial cells. Removing external Na + stimulated 45Ca 2+ efflux ~4-fold and influx ~1.7-fold. The stimulation of efflux was independent of extracellular Ca 2+ and the osmotic Na + substitute. The release of stored Ca 2+, rather than Ca 2+ influx via Na +Ca 2+ exchange, probably causes the increase in [Ca 2+] i and 45Ca 2+ efflux. Cadmium or decreasing external, not intracellular, pH transiently increased [Ca 2+] i. Cd 2+ and some other divalent metals also stimulated 45Ca 2+ efflux. The potency order of the metals that stimulated efflux was Cd 2+ > Co 2+ > Ni 2+ > Fe 2+ > Mn 2+. Incubating the cells with Zn 2+ prior to assaying efflux in the absence of Zn 2+ strongly inhibited the stimulation of 45Ca 2+ efflux by Cd 2+, pH 6, and the removal of external Na + without affecting the stimulation of efflux by ATP. These findings support the hypothesis that certain trace metals or decreasing external Na + or pH trigger the release of stored Ca 2+ by stimulating a cell surface “receptor.”