Hk. Lu et al., ANGIOTENSIN-II STIMULATES T-TYPE CA2-PROTEIN, G(I)( CHANNEL CURRENTS VIA ACTIVATION OF A G), American journal of physiology. Cell physiology, 40(4), 1996, pp. 1340-1349
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.