Ca²⁺ Inactivation of Voltage-Dependent Na⁺ Channels in Cultured Bovine Adrenal Chromaffin Cells: Further Studies on Inhibition of Veratridine-Induced Catecholamine Secretion by External Ca²⁺

Abstract

The stimulatory actions of veratridine (VTD) on catecholamine secretion and Na⁺ influx in cultured bovine adrenal chromaffin cells were studied in the presence of high concentrations of Ca²⁺ in the incubation mixture. Catecholamine secretion evoked by VTD was reduced by elevating the external Ca²⁺ concentration to higher than 2 mM. Under the same conditions, VTD-stimulated ²²Na⁺ uptake into the cells was also reduced by elevating the extracellular Ca²⁺ concentration. In contrast, the secretory action of VTD was not significantly suppressed by preloading Ca2+ to the cells. Furthermore, the effects of extracellular Ca2+ on the sensitivities of the cells to VTD and tetrodotoxin (TTX) were examined, and neither their sensitivities to VTD nor those to TTX were shown to be significantly altered by elevating the Ca2+ concentration in the incubation mixture. These results seem to indicate that the elevation of extracellular Ca2+ concentration may cause the inhibition of VTD-induced catecholamine secretion as a consequence of the inactivation of voltage-dependent Na+ channels, and suggest that Ca2+ may directly act on the cell surface, and the site of Ca2+ action is presumably distinct from the sites of both VTD and TTX actions in the plasma membranes of adrenal chromaffin cells.