Angiotensin II type 1 receptor activation modulates L- and T-type calcium channel activity through distinct mechanisms in bovine adrenal glomerulosa cells

In adrenal zona glomerulosa cells, calcium entry is crucial for aldosterone production and secretion. This influx is stimulated by increases of extrac ellular potassium in the physiological range of concentrations and by angio tensin II (Ang II). The high threshold voltage-activated (L-type) calcium c hannels have been shown to be the major mediators for the rise in cytosolic free calcium concentration, [Ca2+](c), observed in response to a depolaris ation by physiological potassium concentrations. Paradoxically, both T- and L-type calcium channels have been shown to be negatively modulated by Ang II after activation by a sustained depolarisation. While the modulation of T-type channels involves protein kinase C (PKC) activation, L-type channel inhibition requires a pertussis toxin-sensitive G protein. In order to inve stigate the possibility of additional modulatory mechanisms elicited by Ang II on L-type channels, we have studied the effect of PKC activation or tyr osine kinase inhibition. Neither genistein or MDHC, two strong inhibitors o f tyrosine kinases, nor the phorbol ester PMA, a specific activator of PKC, affected the Ang II effect on the [Ca2+](c) response and on the Ba2+ curre nts elicited by cell depolarisation with the patch-clamp method. We propose a model describing the mechanisms of the [Ca2+](c) modulation by Ang II an d potassium in bovine adrenal glomerulosa cells.