Correlates of aldosterone-induced increases in Cai2+ and Isc suggest that Cai2+ is the second messenger for stimulation of apical membrane conductance.

Abstract

Studies were performed on monolayers of cultured A6 cells, grown on permeable filters, to determine the second messenger system involved in the aldosterone-induced increase in electrogenic sodium transport. Addition of aldosterone (1 p&M Invest. 1992. 89:150-156.)

Genomic and nongenomic stimulatory effect of aldosterone on H+-ATPase in proximal S3 segments

“…The present data indicate that the baseline [Ca 2ϩ ] i was 103 Ϯ 2 nM (n ϭ 58), and the stimulatory effect of aldosterone on the H ϩ -ATPase is associated with an increase in [Ca 2ϩ ] i , similar to that observed with angiotensin II (35) and arginine vasopressin (7,24). These results are also in accordance with several authors who found an aldosterone-induced increase in [Ca 2ϩ ] i (10,14,17,19,26,37), indicating that intracellular calcium is a prerequisite for aldosterone action. The increase in [Ca 2ϩ ] i might initiate events that lead to activation of H ϩ -ATPase (16), and the cell acidification stimulates a calciummediated exocytotic insertion of proton pumps, a process important for pH i regulation (34).…”

“…The increase in [Ca 2ϩ ] i might initiate events that lead to activation of H ϩ -ATPase (16), and the cell acidification stimulates a calciummediated exocytotic insertion of proton pumps, a process important for pH i regulation (34). Our results with RU 486 also confirm this behavior since 1) this GR antagonist alone caused a significant decrease in the pHirr and in [ (26). However, the effect of a long-term increase in [Ca 2ϩ ]i is still not adequately explained.…”

Genomic and nongenomic dose-dependent biphasic effect of aldosterone on Na+/H+exchanger in proximal S3 segment: role of cytosolic calcium

“…6 and 7). This could be due to an unspecific inhibitory action of this GR antagonist, but it might also indicate that, in basal conditions, a basal level of aldosterone or some glucocorticoid binding to GR receptors may exist, causing some tonic activation of the Na (11,14,17,19,31,39), indicating that [Ca 2ϩ ] i is a prerequisite for aldosterone action. Nongenomic and pregenomic actions usually involve second messengers, such as inorganic ions, cAMP, or various protein kinases.…”

“…A high-affinity site, which is tonically inhibitory, binds to low Ca 2ϩ /calmodulin, thus suppressing the inhibition, that is, stimulating the exchanger at low Ca 2ϩ / calmodulin levels. A low-affinity site, however, binds with calcium and calmodulin only at high concentrations, and under these conditions inhibits the exchanger activity (26,28,38 (31). However, the effect of a long-term increase in [Ca 2ϩ ] i is still not adequately explained.…”

General – Membrane Transport

“…The role of intracellular Ca2+ ([Ca 2 +];) in regulating amiloride-sensitive epithelial Na+ channels is unclear. In renal epithelia, raising [Ca 2 +]; inhibits apical Na+ channels in rat cortical collecting tubule (Palmer & Frindt, 1987), whereas an early rise in [Ca2+] l governs the increase in apical Na+ channel activity stimulated by aldosterone in A6 renal cells (Petzel et al 1992). We therefore used the dual electrode voltage-clamp technique to assess the effect of raising [Ca2+]l on amiloride-sensitive whole-cell Na+ currents (I~;:-'il) in Xenopus oocytes expressing human renal Na+ channels.…”