Regulation of the Na-K pump of the rat cortical collecting tubule by aldosterone.

Abstract

Activities of Na channels and Na pumps were studied in the rat cortical collecting tubule (CCT) during manipulation of the animals' mineralocorticold status in vivo using a low-Na diet, diuretics, or administration of exogenous aldosterone. Tubules were isolated and split open to expose the luminal membrane surface. Using the whole-cell patch-clamp technique, activities of the apical Na channels and the basolateral Na pumps were measured in principal cells as the currents inhibited by amiloride (10 I.LM) and ouabain (1 raM), respectively. Na channel current (INa) was not measurable in CCTs from control animals on a normal diet. INa was ~ 200 pA/cell in CCTs from animals on a low-Na diet or infused with aldosterone using osmotic minipumps. Currents attributable to the Na pump (/pump) were similar in control animals and animals on a low-Na diet. Maximal currents were ~ 35 pA/cell in both groups, and decreased with hyperpolarization of the cell membrane. In contrast, administration of exogenous aldosterone increased/pump fourfold. Coinfusion of aldosterone and amiloride in vivo through the minipumps did not affect the induction of INa but reduced the induction of/pump by 80%. We conclude that the induction of channel activity in this tissue is a direct action of aldosterone, whereas the induction of pump activity may be a consequence of the increased Na traffic through the epithelial ceils.

Regulation of epithelial Na+channels by adrenal steroids: mineralocorticoid and glucocorticoid effects

“…In that report, the authors argued for an indirect stimulation of the pump protein by aldosterone, secondary to an increase in the rate of Na ϩ entry into the cell across the apical membrane. Subsequent studies in rat CCD supported this conclusion (29). Dexamethasone did not elicit this response, presumably because it did not activate channel-mediated Na ϩ entry.…”

Regulation of renal Na+,K(+)‐ATPase in rat thick ascending limb during K+ depletion: evidence for modulation of Na+ affinity.

“…Based on a recent study in the rat nephron (Palmer, Antonian & Frindt, 1993), a 20 mV hyperpolarization (the maximum which might be expected in the MTAL of LK-14 rats) would reduce the Na+,K+ pump by about 20 %, which is not nearly enough to account for the 50% inhibition of the Na+,K+ pump observed in the MTAL of LK-14 rats (Fig. 4B), given that its Vmax was increased by 30-50% (Fig.…”

Regulation of Na channels of the rat cortical collecting tubule by aldosterone.

“…8 can be described by a simple doseresponse relationship between aldosterone concentration and channel activity, with an apparent Kd for activation of ~ 8 nM. However, results in the companion paper (Palmer, Antonian, and Frindt, 1993) suggest that the relationship between aldosterone concentration and channel activity may be steeper than that predicted from this simple hyperbola. In either case the data are consistent with the operation of a highaffinity receptor system with a Ks in the nanomolar range, corresponding to the type I or mineralocorticoid receptor (Rossier, Geering, Atkinson, and Roch-Ramel, 1985).…”