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

Abstract

The activity of apical membrane Na channels in the rat cortical collecting tubule was studied during manipulation of the animals' mineralocorticoid status in vivo using a low-Na diet or the diuretic furosemide. Tubules were isolated and split open to expose the luminal membrane surface. Induction of Na channel activity was studied in cell-attached patches of the split tubules. No activity was observed with control animals on a normal diet. Channel activity could be induced by putting the animals on the low-Na diet for at least 48 h. The mean number of open channels per patch (NPo) was maximal after 1 wk on low Na. Channels were also induced within 3 h after injection of furosemide (20 mg/kg body wt per d). NPo was maximal 48 h after the first injection. In both cases, increases in NPo were primarily due to increases in the number of channels per patch (N) at a constant open probability (Po). With salt depletion or furosemide injection NPo is a saturable function of aldosterone concentration with half-maximal activity at ~ 8 nM. When animals were salt repleted after 1-2 wk of salt depletion, both plasma aldosterone and NPo fell markedly within 6 h. NPo continued to decrease over the next 14 h, while plasma aldosterone rebounded partially. Channel activity may be dissociated from aldosterone concentrations under conditions of salt repletion.

Hyperaldosteronemia and Activation of the Epithelial Sodium Channel Are Not Required for Sodium Retention in Puromycin-Induced Nephrosis

“…Although this disagrees somehow with previous studies that reported no active ENaC in control Na ϩ -replete rats (18), it is worth noting that the frequency of ENaC remained low and the number of channels per patch was always Յ4. As previously reported (18,19), the frequency of patches with ENaC increased greatly in Na ϩ -depleted rats (12 of 27, 44.4%), and the number of channels per patch was Ͼ4 in two of three of the patches. The situation was intermediate in CCD from PAN-nephrotic rats, with 18.6% of patches (eight of 43) that contained ENaC and 50% of the patches with more than four channels.…”

Aldosterone Activates NF-κB in the Collecting Duct

“…38 -40 Although NF-B-inducible reporter gene was activated in response to aldosterone concentrations as low as 10 Ϫ10 M in cultured CD cells, enhanced proinflammatory gene expression was observed in response to supraphysiologic concentrations of aldosterone in cultured cells and freshly isolated CCD; however, aldosterone-induced NF-B activation observed in CD cells might be relevant to physiopathologic conditions. Indeed, rats under low-Na diet, which classically exhibit high aldosterone circulating levels, 41 exhibit increased expression levels of several NF-B-induced genes, and hyperaldosteronism is frequently observed in both experimental nephropathies 42 and in human chronic renal failure. 43,44 Results obtained in CCD from rats under low-Na diet and evidence obtained in cultured nonclassical aldosterone-responsive proximal tubular cells 45 or glomerular mesangial cells 12 strongly suggest that aldosterone may induce or enhance tubulointerstitial and glomerular BASIC RESEARCH www.jasn.org inflammation and fibrosis via NF-B activation.…”

Ras Pathway Activates Epithelial Na+Channel and Decreases Its Surface Expression inXenopusOocytes

“…On readdition of the hormone, the P o returned to "normal", that is, long open and closed periods with a mean P o between 0.24 and 0.38; however, it appears that low P o of the epithelial Na ϩ channel is not observed in other situations, and hence other authors only saw the appearance of "new channels" with a P o similar to the preexisting ones (if there were preexisting ones) on treatment of A6 epithelia with aldosterone or rats with low-sodium diet (Pácha et al, 1993;Helman et al, 1998). These latter results support the hypothesis that a population of surface channels is switched from a silent mode to an active one by aldosterone or that intracellular channels are translocated to the cell surface.…”