Angiotensin II stimulates T-type Ca2+ channel currents via activation of a G protein, Gi.
Angiotensin II (ANG II) is the most potent and the most physiologically important stimulator of aldosterone synthesis and secretion from the adrenal zona glomerulosa. Because steroidogenesis by adrenal glomerulosa (AG) cells 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 type 1 receptor. The effect of the hormone is not mediated by Ca2+/calmodulin-dependent protein kinase II (CaMKII) 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 monoclonal 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.
Department of Pharmacology, University of Virginia, Charlottesville 22908, USA.
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Lu
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Fern
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Luthin
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Linden
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Liu
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Cohen
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Barrett
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D004553:Electric Conductivity; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D011945:Receptors, Angiotensin / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000502:physiology*
D015220:Calcium Channels; D011945:Receptors, Angiotensin; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D037342:Pertussis Toxin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium