Rapid activation of KATP channels by aldosterone in principal cells of frog skin.

1. In epithelial cells of frog skin, potassium ions are recycled across the basolateral membrane via an inward-rectifier, ATP-sensitive K+ channel (KATP channel). In this study, we show that aldosterone has a stimulatory effect on KATP channel activity and we have investigated the involvement of Na+-H+ exchange and intracellular pH (pHi) in this phenomenon. 2. Aldosterone (10 nM) produced an increase in the open probability of the KATP channel within 15 min from 0.21 +/- 0.05 to 0.93 +/- 0.10 (n = 8), measured in cell-attached patches. Aldosterone also increased the tolbutamide-sensitive K+ current across the basolateral membrane within 30 min from 17.2 +/- 1.9 to 30.3 +/- 1.6 microA cm-2 (n = 8) in nystatin-permeabilized whole skins. 3. The KATP channel is very sensitive to variations in cytosolic pH within the physiological range 7.0-7.4. 4. The intracellular pH of principal cells is regulated by Na+-H+ exchange, and the stimulatory effect of aldosterone on KATP channel activity was abolished by amiloride (100 microM) added on the basolateral side of the epithelium either before or after aldosterone treatment. 5. We propose that aldosterone activates the KATP channels via stimulation of Na+-H+ exchange. The rapidity of aldosterone activation of KATP channels is presented as evidence for a novel non-genomic steroid hormone effect on epithelial ion transport.