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

Abstract

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 + 1P9 to 30 3 + 1-6 1A cm2 (n = 8) in nystatinpermeabilized 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 uM) 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.

The Glycolytic Enzymes, Glyceraldehyde-3-phosphate Dehydrogenase, Triose-phosphate Isomerase, and Pyruvate Kinase Are Components of the KATP Channel Macromolecular Complex and Regulate Its Function

“…There is evidence to suggest that functional compartmentalization of ATP may be involved in receptor signaling, for example, the angiotensin II-mediated closure of cardiac K ATP channels (44). There is also a curious functional interaction between K ATP channels and the Na ϩ /K ϩ pump, whereby the activity of one determines the activity of the other, most likely by competition for the same glycolytically derived ATP (45)(46)(47)(48)(49). K ATP channels in vascular smooth muscle and glial cells have Kir6.1 as the pore forming subunit (1), which also interacts with GAPDH and PK.…”

Nongenomic stimulation of vacuolar H + -ATPases in intercalated renal tubule cells by aldosterone

“…Several nongenomic effects of aldosterone have been described (17,(37)(38)(39). These involve rapid modulations of epithelial Na and K channel activity and of Na͞H exchange (40,41). Representative examples are stimulation of Na ϩ ͞H ϩ exchanger by aldosterone in colon crypt cells, the Madin-Darby canine kidney cell line, and vascular smooth muscle cells (40,42,43).…”

Mechanisms Underlying Rapid Aldosterone Effects in the Kidney

“…The conclusion based on these data is that GR is responsible for transducing an early nongenomic [ response but a suppression of NHE activity to less than basal levels rather than the stimulation seen at lower concentrations. Modulation of NHE activity by aldosterone may also contribute to the activation of pHsensitive K + ATP channels in the basolateral membrane to promote K + recycling (113). Other mechanisms for the regulation of apical K + channel activity rely upon elevated SGK1 activity either to suppress Nedd4-2, which ubiquitinates KCNQ2-and KCNQ3-type K + channels (114,115), or to modulate ROMK activity through direct phosphorylation of WNK4 by SGK1 (14).…”