Duality of the voltage-dependent calcium influx in adrenal glomerulosa cells.
Both T- and L-type calcium channels are expressed in bovine adrenal glomerulosa cells and both channels are sensitive to moderate depolarizations of the cell membrane induced by angiotensin II (AngII) or physiological concentrations of extracellular K+. These channels present distinct pharmacology, L-type channels being more sensitive to dihydropyridines, whereas T channels are inhibited by lower concentrations of mibefradil, a new type of calcium antagonist currently used for treating hypertension. The activity of these channels is also differently modulated by AngII, which inhibits T channels through activation of protein kinase C and L channels through a Pertussis toxin-sensitive G protein. Finally, whereas the activity of L-type channels is directly reflected on the levels of the cytosolic calcium concentration ([Ca2+]c), T-type channels are more closely related to the control of steroidogenesis, possibly through a kind of "calcium pipeline" linking the plasma membrane to the mitochondria. In conclusion, two types of calcium channels, with distinct functions and differential modulation by AngII, are activated by agonists of aldosterone biosynthesis in adrenal glomerulosa cells. Most importantly, these channels have distinct sensitivities to currently used antihypertensive therapeutic drugs.
Rossier
M F
MF
Division of Endocrinology & Diabetology, University Hospital, Geneva, Switzerland.
Burnay
M M
MM
Maturana
A
A
Capponi
A M
AM
D000450:Aldosterone / Q000819:agonists; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D002417:Cattle; D002478:Cells, Cultured; D004594:Electrophysiology; D013268:Stimulation, Chemical; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D000804:Angiotensin II; D000450:Aldosterone