Nongenomic regulation of ENaC by aldosterone.
Aldosterone is involved in salt and water homeostasis. The main effect is thought to involve genomic mechanisms. However, the existence of plasma membrane steroid receptors has been postulated. We used whole cell patch clamp to test the hypothesis that epithelial sodium channels (ENaC) expressed by renal collecting duct principal cells can be regulated nongenomically by aldosterone. In freshly isolated principal cells from rabbit, aldosterone (100 nM) rapidly (<2 min) increased ENaC sodium current specifically. The aldosterone-activated current was completely inhibited by amiloride. Aldosterone also activated ENaC in cells treated with the mineralocorticoid receptor blocker spiranolactone. Nongenomic activation was inhibited by inclusion of S-adenosyl-L-homocysteine in the pipette solution, which inhibits methylation reactions. Also, the nongenomic activation required 2 mM ATP supplementation in the pipette solution. Aldosterone did not activate any ENaC current in whole cell clamped rat collecting duct principal cells. These functional studies are consistent with aldosterone membrane binding studies, suggesting the presence of a plasma membrane steroid receptor that affects cellular processes by mechanisms unrelated to altered gene expression.
Zhou
Z H
ZH
Department of Physiology & Biophysics, University of Alabama at Birmingham, 35294, USA.
Bubien
J K
JK
D000450:Aldosterone / Q000378:metabolism* / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D053503:Epithelial Sodium Channels; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000166:cytology; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D018408:Patch-Clamp Techniques; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D004232:Diuretics; D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D012076:Renal Agents; D015222:Sodium Channels; D013873:Thionucleotides; D014667:Vasopressins; D013148:Spironolactone; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium; D000242:Cyclic AMP