EFFECTS OF HIGH POTASSIUM CONCENTRATION AND DIHYDROPYRIDINE CA-2+-CHANNEL AGONISTS ON CYTOPLASMIC CA-2+ AND ALDOSTERONE PRODUCTION IN RAT ADRENAL GLOMERULOSA CELLS

The aldosterone secretory response of isolated rat adrenal glomerulosa cells to potassium was studied in a cell-perifusion system. Increasing the potassium concentration from 3.6 to 5.4 mM in the perifusion medium caused a rapid 40-fold stimulation of aldosterone production which was maintained during the 2 h period of stimulation. a dose of 8.4 mM potassium elicited a 100-fold increase of hormone production with rapid onset and a slowly decreasing plateau. When the potassium concentration was further increased to 18 mM, there was a rapid stimulation of aldosterone production comparable to that evoked by 8.4 mM potassium; however, the response declined very rapidly to levels still above basal. The dihydropyridine-agonist bay-k 8644 (100 nM) greatly enhanced the aldosterone response to 5.4 mM potassium but did not significantly modify the response evoked by 8.4 mM potassium. The effect of bay-k 8644 on the aldosterone response was inhibitory at 18 mM potassium concentration, suggesting that the character of dihydropyridine modulation of the secretory response was voltage dependent, showing reversal at rela- tively negative potentials. When the cytoplasmic Ca2+concentration was monitored in glomerulosa cells by the fluorescent Ca2+-probe Fura-2, potassium evoked a rapid dose-dependent increase in free Ca2+, with elevated steady-state Ca2+-levels throughout stimulation, even at potassium concentrations higher than 18 mM. Moreover, bay-k 8644 (100 nM) enhanced the cytoplasmic Ca2+response to all potassium concentrations tested up to 30 mM. The initial 30 sec 46Ca2+uptake, an indicator of potassium-stimulated voltage-sensitive Ca2+influx into these cells, showed a fast increase and only an initial inactivation in response to 18 mM potassium. This response was enhanced by 100 nM bay-k 8644, with no sign of enhanced inactivation or inhibition caused by the dihydropyridine agonist. These results indicate that the correlation between Ca2+influx, cytoplasmic Ca2+levels, and the secretory response in adrenal glomerulosa cells is lost at potassium concentrations higher than 8 mM, especially in the presence of the dihydropyridine agonist, bay-k 8644. © 1990 by The Endocrine Society.