ROLE OF THE CAPACITATIVE CALCIUM INFLUX IN THE ACTIVATION OF STEROIDOGENESIS BY ANGIOTENSIN-II IN ADRENAL GLOMERULOSA CELLS

Angiotensin-II (AngII)-induced Ca2+ influx in adrenal glomerulosa cell s, a signal necessary for the stimulation of steroidogenesis by the ho rmone, is believed to involve two distinct mechanisms: 1) opening of v oltage-operated Ca2+ channels, and 2) activation of a capacitative Ca2 + entry pathway that is dependent on calcium release from intracellula r stores. Nicardipine, a dihydropyridine calcium antagonist, has been used to investigate the role of these Ca2+ entry mechanisms in the ste roidogenic response to AngII. As demonstrated with the patch-clamp tec hnique, micromolar concentrations of nicardipine completely blocked vo ltage-operated Ca2+ channel activity of both T- and L-types. This agen t similarly inhibited the rise of cytosolic free calcium concentration induced by potassium, but did not significantly affect the response t o thapsigargin, an activator of the capacitative pathway. Nicardipine reduced by only 22% the calcium influx stimulated by AngII, and the ni cardipine-insensitive part of this response was abolished after exhaus ting the intracellular Ca2+ stores with thapsigargin. Similarly, aldos terone secretion induced by AngII was only partially inhibited (40%) b y nicardipine at concentrations that completely abolished the steroido genic response to potassium. Thapsigargin by itself was able to stimul ate aldosterone production, an action highly potentiated by physiologi cal concentrations of extracellular potassium. These data strongly sug gest that the major part of the calcium influx response to AngII, lead ing to aldosterone formation, involves a capacitative calcium entry pa thway activated by the release of calcium from intracellular stores. T his mechanism of calcium influx could be responsible for some features of aldosterone response to the hormone, such as its poor sensitivity to dihydropyridines or its potentiation by potassium.