ANGIOTENSIN-II STIMULATES T-TYPE CA2-PROTEIN, G(I)( CHANNEL CURRENTS VIA ACTIVATION OF A G)

Angiotensin II (ANG II) is the most potent and the most physiologicall y important stimulator of aldosterone synthesis and secretion from the adrenal zona glomerulosa. Because steroidogenesis by adrenal glomerul osa (AG) cells is mediated in part by Ca2+ influx through T- and L-typ e Ca2+ channels, we evaluated whether T-type Ca2+ channels are regulat ed by ANG II. We observe that ANG II enhances T-type Ca2+ current by s hifting the voltage dependence of channel activation to more negative potentials. This shift is transduced by the ANG II type 1 receptor. Th e effect of the hormone is not mediated by Ca2+/calmodulin-dependent p rotein kinase II (CaMKII) as it is not prevented by CaMKII((281-302)), a peptide inhibitor of the catalytic region of the kinase. Rather, th is shift is mediated by the activation of a G protein, G(i), because i t is abolished by cell pretreatment with pertussis toxin and by cell d ialysis with a monoclonal antibody generated against recombinant G(i) alpha. This effect of ANG II on T-type Ca2+ channels should increase C a2+ entry in AG cells at physiologically relevant voltages and result in a sustained increase in aldosterone secretion.