Abstract

Three divalent cations can elicit secretory responses in most neuroendocrine cells, including chromaffin cells. The extent to which secretion is elicited by the cations in intact depolarized cells was Ba²⁺ > Sr²⁺ ≥ Ca²⁺, contrasting with that elicited by these cations in permeabilized cells (Ca²⁺ > Sr²⁺ > Ba²⁺). Current-clamp recordings show that extracellular Sr²⁺ and Ba²⁺ cause membrane depolarization and action potentials, which are not blocked by Cd²⁺ but that can be mimicked by tetra-ethyl-ammonium. When applied intracellularly, only Ba²⁺ provokes action potentials. Voltage-clamp monitoring of Ca²⁺-activated K⁺ channels (K_Ca) shows that Ba²⁺ reduces outward currents, which were enhanced by Sr²⁺. Extracellular Ba²⁺ increases cytosolic Ca²⁺ concentrations in Fura-2-loaded intact cells, and it induces long-lasting catecholamine release. Conversely, amperometric recordings of permeabilized cells show that Ca²⁺ promotes the longest lasting secretion, as Ba²⁺ only provokes secretion while it is present and Sr²⁺ induces intermediate-lasting secretion. Intracellular Ba²⁺ dialysis provokes exocytosis at concentrations 100-fold higher than those of Ca²⁺, whereas Sr²⁺ exhibits an intermediate sensitivity. These results are compatible with the following sequence of events: Ba²⁺ blocks K_Ca channels from both the outside and inside of the cell, causing membrane depolarization that, in turn, opens voltage-sensitive Ca²⁺ channels and favors the entry of Ca²⁺ and Ba²⁺. Although Ca²⁺ is less permeable through its own channels, it is more efficient in triggering exocytosis. Strontium possesses both an intermediate permeability and an intermediate ability to induce secretion.