Ca2+ influx and clearance at hyperpolarized membrane potentials modulate spontaneous and stimulated exocytosis in neuroendocrine cells

Autor: Alla F. Fomina, Lukun Yang
Rok vydání: 2020
Předmět:
Zdroj: Cell Calcium. 87:102184
ISSN: 0143-4160
DOI: 10.1016/j.ceca.2020.102184
Popis: Neuroendocrine adrenal chromaffin cells release neurohormones catecholamines in response to Ca2+ entry via voltage-gated Ca2+ channels (VGCCs). Adrenal chromaffin cells also express non-voltage-gated channels, which may conduct Ca2+ at negative membrane potentials, whose role in regulation of exocytosis is poorly understood. We explored how modulation of Ca2+ influx at negative membrane potentials affects basal cytosolic Ca2+ concentration ([Ca2+]i) and exocytosis in metabolically intact voltage-clamped bovine adrenal chromaffin cells. We found that in these cells, Ca2+ entry at negative membrane potentials is balanced by Ca2+ extrusion by the Na+/Ca2+ exchanger and that this balance can be altered by membrane hyperpolarization or stimulation with an inflammatory hormone bradykinin. Membrane hyperpolarization or application of bradykinin augmented Ca2+-carrying current at negative membrane potentials, elevated basal [Ca2+]i, and facilitated synchronous exocytosis evoked by the small amounts of Ca2+ injected into the cell via VGCCs (up to 20 pC). Exocytotic responses evoked by the injections of the larger amounts of Ca2+ via VGCCs (> 20 pC) were suppressed by preceding hyperpolarization. In the absence of Ca2+ entry via VGCCs and Ca2+ extrusion via the Na+/Ca2+ exchanger, membrane hyperpolarization induced a significant elevation in [Ca2+]i and asynchronous exocytosis. Our results indicate that physiological interferences, such as membrane hyperpolarization and/or activation of non-voltage-gated Ca2+ channels, modulate basal [Ca2+]i and, consequently, segregation of exocytotic vesicles and their readiness to be released spontaneously and in response to Ca2+ entry via VGCCs. These mechanisms may play role in homeostatic plasticity of neuronal and endocrine cells.
Databáze: OpenAIRE
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