HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/F966    most recent 90475.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Fodstad, H. Articles by Horisberger, J.-D. Search for Related Content PubMed PubMed Citation Articles by Fodstad, H. Articles by Horisberger, J.-D.

Effects of mineralocorticoid and K⁺ concentration on K⁺ secretion and ROMK channel expression in a mouse cortical collecting duct cell line

Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland

Submitted 8 August 2008 ; accepted in final form 10 March 2009

The cortical collecting duct (CCD) plays a key role in regulated K⁺ secretion, which is mediated mainly through renal outer medullary K⁺ (ROMK) channels located in the apical membrane. However, the mechanisms of the regulation of urinary K⁺ excretion with regard to K⁺ balance are not well known. We took advantage of a recently established mouse CCD cell line (mCCD_cl1) to investigate the regulation of K⁺ secretion by mineralocorticoid and K⁺ concentration. We show that this cell line expresses ROMK mRNA and a barium-sensitive K⁺ conductance in its apical membrane. As this conductance is sensitive to tertiapin-Q, with an apparent affinity of 6 nM, and to intracellular acidification, it is probably mediated by ROMK. Overnight exposure to 100 nM aldosterone did not significantly change the K⁺ conductance, while it increased the amiloride-sensitive Na⁺ transport. Overnight exposure to a high K⁺ (7 mM) concentration produced a small but significant increase in the apical membrane barium-sensitive K⁺ conductance. The mRNA levels of all ROMK isoforms measured by qRT-PCR were not changed by altering the basolateral K⁺ concentration but were decreased by 15–45% upon treatment with aldosterone (0.3 or 300 nM for 1 and 3 h). The paradoxical response of ROMK expression to aldosterone could possibly work as a preventative mechanism to avoid excessive K⁺ loss which would otherwise result from the increased electrogenic Na⁺ transport and associated depolarization of the apical membrane in the CCD. In conclusion, mCCD_cl1 cells demonstrate a significant K⁺ secretion, probably mediated by ROMK, which is not stimulated by aldosterone but increased by overnight exposure to a high K⁺ concentration.

cultured mCCD cells; urinary potassium excretion; aldosterone