Angiotensin ii stimulates t-type calcium channel currents in
adrenal glomerulosa cells via activation of a g protein, gi.
Lu, Hong-Kai, Robert J. Fern, David Luthin, Li-Ping Liu, Charles J.
Cohen, and Paula Q. Barrett.
Departments of Pharmacology and Medicine, University of Virginia,
Charlottesville, Virginia 22908 and Department of Membrane
Biochemistry and Biophysics, Merck Research Laboratories, Rahway, New
Jersey 07065
APStracts 3:0135C, 1996.
Angiotensin II (Ang II) is the most potent and physiologically the
most important stimulator of aldosterone synthesis and secretion from
the adrenal zona glomerulosa. Since steroidogenesis by adrenal
glomerulosa cells (AG) is mediated in part by Ca2+ influx through T-
and L-type Ca2+ channels, we evaluated whether T-type Ca2+ channels
are regulated by Ang II. We observe that Ang II enhances T-type Ca2+
current by shifting the voltage dependence of channel activation to
more negative potentials. This shift is transduced by the Ang II AT1
-receptor. The effect of the hormone is not mediated by
Ca2+/calmodulin-dependent protein kinase II (CaMKinase II) as it is
not prevented by CaMKII(281-302), a peptide inhibitor of the
catalytic region of the kinase. Rather, this shift is mediated by the
activation of a G protein, Gi, because it is abolished by cell
pretreatment with pertussis toxin and by cell dialysis with a
monclonal antibody generated against recombinant Gi[alpha]. This
effect of Ang II on T-type Ca2+ channels should increase Ca2+ entry
in AG cells at physiologically relevant voltages and result in a
sustained increase in aldosterone secretion.
Received 22 January 1996; accepted in final form 3 April 1996.
APS Manuscript Number C46-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96