Relative roles of sodium and calcium ions in the steroidogenic response of isolated rate adrenal glomerulosa cells.

To study the relative roles of sodium (Na+) and calcium ions (Ca2+) in the response of adrenal glomerulosa cells, we investigated the effects of different Na+ concentrations in the incubation media and the actions of substances that interfere with Ca2+ fluxes. Basal aldosterone secretion and response to angiotensin II (AII), adrenocorticotropic hormone (ACTH), or potassium (K+) were dependent on extracellular Na+ concentration. Veratridine, a Na+ channel opener that dissipates Na+ gradients, blocked the stimulated steroidogenic response. Mersalyl acid and tetracaine, which are potent Ca2+ antagonists, blocked the effects of aldosterone secretagogues. Divalent cations with Ca2+ antagonistic action such as manganese M(n2+), nickel (Ni2+), and cobalt (Co2+) blocked the aldosterone secretory response to AII, ACTH, and K+. Barium (Ba2+) and strontium (Sr2+), known to mimick Ca2+ effects, increased or did not affect responses of the glomerulosa cells. Sodium vanadate, an inhibitor of ATP-dependent Ca2+ translocation, did not alter the stimulated aldosterone responses. Trifluoperazine (10(-6) M), an inhibitor of calmodulin, blocked AII and K+-induced aldosterone secretion, but was partially effective on ACTH-stimulated aldosterone output only at a concentration of 10(-5) M. The actions of ouabain on aldosterone biosynthesis were similarly affected by all these drugs. Thus, both extracellular Na+ and Ca2+ appear to play a role in the steroidogenic response of isolated glomerulosa cells. The intracellular action of Ca2+ may involve a calmodulin-like protein. The effects of ACTH are only partially dependent on Ca2+ as a second intracellular messenger.