Abstract
The actions of the protonophore CCCP on intracellular Ca 2+ regulation and exocytosis in chromaffin cells have been examined. Simultaneous fura-2 imaging and amperometry reveal that exposure to CCCP not only perturbs mitochondrial function but that it also alters vesicular storage of Ca 2+ and catecholamines. By disrupting the pH gradient of the secretory vesicle membrane, the protonophore allows both Ca 2+ and catecholamine to leak into the cytosol. Unlike the high cytosolic Ca 2+ concentrations resulting from mitochondrial membrane disruption, Ca 2+ leakage from secretory vesicles may initiate exocytotic release. In conjunction with previous studies, this work reveals that catalytic and self-sustained vesicular Ca 2+-induced exocytosis occurs with extended exposure to weak acid or base protonophores.
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