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Pflugers Arch. 2018 Oct;470(10):1459-1471. doi: 10.1007/s00424-018-2166-4. Epub 2018 Jun 21.

Distinct patterns of exocytosis elicited by Ca2+, Sr2+ and Ba2+ in bovine chromaffin cells.

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Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029, Madrid, Spain.
Unidad de Farmacología, Facultad de Medicina, Universidad de La Laguna, 38200, La Laguna, Tenerife, Spain.
Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
INTEGRARE, Généthon, Inserm, Univ Evry, Université Paris-Saclay, 91002, Evry, France.
Unidad de Farmacología, Facultad de Medicina, Universidad de La Laguna, 38200, La Laguna, Tenerife, Spain.
Instituto Universitario de BioOrgánica Antonio González, Universidad de La Laguna, 38200, La Laguna, Tenerife, Spain.


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 (KCa) 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 KCa 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.


Adrenal medulla; Amperometry; Catecholamines; Secretion

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