1. In epithelial cells of frog skin, potassium ions are recycled acros
s the basolateral membrane via an inward-rectifier, ATP-sensitive K+ c
hannel (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 thi
s 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 a
lso increased the tolbutamide-sensitive K+ current across the basolate
ral 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 physiologi
cal range 7.0-7.4. 4. The intracellular pH of principal cells is regul
ated 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 aldoster
one treatment. 5. We propose that aldosterone activates the K-ATP chan
nels via stimulation of Na+-H+ exchange. The rapidity of aldosterone a
ctivation of K-ATP channels is presented as evidence for a novel. non-
genomic steroid hormone effect on epithelial ion transport.