Rapid activation of K-ATP 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 (K-ATP channel). In this study, we show that aldosterone has a stimulatory effect on K-ATP channel activity and we have investigated the involvement of Na+-H+ exchange and intracellular pH (pH(i)) in this phenomenon. 2. Aldosterone (10 nM) produced an increase in the open probability of the K-ATP 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 mu A cm(-2) (n = 8) in nystatin-permeabilized whole skins. 3. The K-ATP 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 K-ATP channel activity was abolished by amiloride (100 mu M) added on the basolateral side of the epithelium either before or after aldosterone treatment. 5. We propose that aldosterone activates the K-ATP channels via stimulation of Na+-H+ exchange. The rapidity of aldosterone activation of K-ATP channels is presented as evidence for a novel. non-genomic steroid hormone effect on epithelial ion transport.