Mobilizing store Ca2+ in the presence of La3+ evokes exocytosis in bovine chromaffin cells

The effect on exocytosis of La3+, a known inhibitor of plasma membrane Ca2+-ATPases and Na+/Ca2+ exchangers, was studied using cultured bovine adrenal chromaffin cells. At high concentrations (0.3-3 mM), La3+ substantially increased histamine-induced catecholamine secretion. This action was mimicked by other lanthanide ions (Nd3+, Eu3+, Gd3+, and Tb3+), but not several divalent cations, In the presence of La3+, the secretory response to histamine became independent of extracellular Ca2+. La3+ enhanced secretion evoked by other agents that mobilize intracellular Ca2+ stores (angiotensin II, bradykinin, caffeine, and thapsigargin), but not that due to passive depolarization with 20 mM K+. La3+ still enhanced histamine-induced secretion in the presence of the nonselective inhibitors of Ca2+-permeant channels SKF96365 and Cd2+, but the enhancement was abolished by prior depletion of intracellular Ca2+ stores with thapsigargin. La3+ inhibited Ca-45(2+) efflux from preloaded chromaffin cells in the presence or absence of Na+. It also enhanced and prolonged the rise in cytosolic [Ca2+] measured with fura-2 during mobilization of intracellular Ca2+ stores with histamine in Ca2+-free buffer. The results suggest that the efficacy of intracellular Ca2+ stores in evoking exocytosis is enhanced dramatically by inhibiting Ca2+ efflux from the cell.