The mechanism of Ba2+ ‐induced exocytosis from single chromaffin cells

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Abstract
Dialysis of Ba2+ into voltage‐clamped single bovine chromaffin cells produced a concentration‐dependent increase in cell capacitance, reflecting an enhanced rate of exocytotic events. Between 0.1 and 1 mM, Ba2+ linearly increased both the rate and the total amount of exocytosis. In undamped cells also, extracellular Ba2+ induced the release of catecholamines, as assayed with a carbon‐fibre electrode in the amperometric mode. Additionally, extracellular application of Ba2+ increased the apparent internal Ca2+ concentration ([Ca2+]app) in fura‐2‐loaded chromaffin cells. These observations were made both in the presence and absence of external Ca2+ (Ca2+ 0), as well as after depletion of the intracellular Ca2+ stores with ionomycin. Under current‐clamp conditions, Ba2+ induced pronounced depolarization of the cells. These results are compatible with the following conclusions: by blocking K+ channels, Ba2+ causes depolarization of chromaffin cells. This results in opening of voltage‐gated Ca2+ channels and Ba2+ entry into the cytosol. Ba2+ then directly triggers exocytotic events, although it induces exocytosis only at concentrations more than a 100‐fold higher than Ca2+. Various effects contribute to the generally observed greater secretory responses with Ba2+ as compared with Ca2+; these are the depolarizing effects of extracellular Ba2+, its greater entry through non‐inactivating Ca2+ channels and its poor intracellular buffering largely arising from its weak affinity for plasmalemmal Ca2+ extrusion mechanisms. In some cases, Ba2+ additionally induces release of Ca2+ from internal stores, as evidenced by its effect on fura‐2 fluorescence at different wavelengths.