Distinct patterns of exocytosis elicited by Ca, Sr and Ba in bovine chromaffin cells.

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 Ba > Sr ≥ Ca, contrasting with that elicited by these cations in permeabilized cells (Ca > Sr > Ba). Current-clamp recordings show that extracellular Sr and Ba cause membrane depolarization and action potentials, which are not blocked by Cd but that can be mimicked by tetra-ethyl-ammonium. When applied intracellularly, only Ba provokes action potentials. Voltage-clamp monitoring of Ca-activated K channels (K) shows that Ba reduces outward currents, which were enhanced by Sr. Extracellular Ba increases cytosolic Ca concentrations in Fura-2-loaded intact cells, and it induces long-lasting catecholamine release. Conversely, amperometric recordings of permeabilized cells show that Ca promotes the longest lasting secretion, as Ba only provokes secretion while it is present and Sr induces intermediate-lasting secretion. Intracellular Ba dialysis provokes exocytosis at concentrations 100-fold higher than those of Ca, whereas Sr exhibits an intermediate sensitivity. These results are compatible with the following sequence of events: Ba blocks K channels from both the outside and inside of the cell, causing membrane depolarization that, in turn, opens voltage-sensitive Ca channels and favors the entry of Ca and Ba. Although Ca 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.