Regulation of angiotensin II-stimulated Ca2+ oscillations by Ca2+ influx mechanisms in adrenal glomerulosa cells.

In adrenal glomerulosa cells, angiotensin II (Ang II) evokes repetitive [Ca2+]i transients and increases Ca2+ influx through voltage-sensitive calcium channels (VSCCs) as well as the capacitative Ca2+ entry pathway. This study analyzed the relationships between these Ca2+ influx pathways and intracellular Ca2+ signaling in bovine glomerulosa cells, in which Ca2+ oscillation frequency was regulated by Ang II concentration over the range of 50-300 p. In the absence of external Ca2+, such oscillations were maintained for prolonged periods of time, but their frequency was significantly reduced (0.23 min-1 versus 0.38 min-1). Restoration of [Ca2+]o to 0.6 mM increased the frequency of Ca2+ oscillations in cells that showed narrow spikes of constant amplitude and caused a plateau response in cells with broad spikes of rapidly decreasing amplitude. In the presence of Ca2+, nifedipine reduced the frequency of the oscillatory Ca2+ response to 100 pM Ang II by 49%, and BAY K 8644 increased oscillation frequency by 86%, or caused plateau-type responses typical of higher Ang II concentrations. In contrast to their prominent actions on Ca2+ spiking frequency, dihydropyridines caused only minor changes in Ang II (100 pM)-induced inositol phosphate production. Dihydropyridines also had minimal effects on the nonoscillatory Ca2+ signals evoked by high Ang II concentrations (10 nM). These findings indicate that Ca2+ influx through VSCCs modulates the frequency of Ca2+ oscillations induced by low agonist concentrations by a mechanism that does not involve major changes in inositol trisphosphate formation. However, VSCCs make relatively little contribution to the nonoscillatory Ca2+ signals generated by high agonist concentrations, when Ca2+ influx occurs predominantly through the capacitative Ca2+ entry pathway.