2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2007040443v1 19/4/731    most recent 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 Google Scholar Articles by Wildman, S. S.P. Articles by Unwin, R. J. PubMed PubMed Citation Articles by Wildman, S. S.P. Articles by Unwin, R. J.

Sodium-Dependent Regulation of Renal Amiloride-Sensitive Currents by Apical P2 Receptors

Scott S.P. Wildman^*,, Joanne Marks, Clare M. Turner, Liang Yew-Booth, Claire M. Peppiatt-Wildman, Brian F. King, David G. Shirley, WenHui Wang and Robert J. Unwin

^* Department of Veterinary Basic Sciences, The Royal Veterinary College, and Department of Physiology and Centre for Nephrology, University College London, London, United Kingdom; and Department of Pharmacology, New York Medical College, Valhalla, New York, New York

Correspondence: Dr. Scott S.P. Wildman, Department of Veterinary Basic Sciences, Royal Veterinary College, Camden Campus, Royal College Street, London NW1 0TU, UK. Phone: +44-0-20-7121-1903; Fax: +44-0-20-7468-5204; E-mail: swildman{at}rvc.ac.uk

Received for publication April 13, 2007. Accepted for publication November 21, 2007.

The epithelial sodium channel (ENaC) plays a major role in the regulation of sodium balance and BP by controlling Na⁺ reabsorption along the renal distal tubule and collecting duct (CD). ENaC activity is affected by extracellular nucleotides acting on P2 receptors (P2R); however, there remain uncertainties over the P2R subtype(s) involved, the molecular mechanism(s) responsible, and their physiologic role. This study investigated the relationship between apical P2R and ENaC activity by assessing the effects of P2R agonists on amiloride-sensitive current in the rat CD. Using whole-cell patch clamp of principal cells of split-open CD from Na⁺-restricted rats, in combination with immunohistochemistry and real-time PCR, we found that activation of metabotropic P2R (most likely the P2Y₂ and/or ₄ subtype), via phospholipase C, inhibited ENaC activity. In addition, activation of ionotropic P2R (most likely the P2X₄ and/or _4/6 subtype), via phosphatidylinositol-3 kinase, either inhibited or potentiated ENaC activity, depending on the extracellular Na⁺ concentration; therefore, it is proposed that P2X₄ and/or _4/6 receptors might function as apical Na⁺ sensors responsible for local regulation of ENaC activity in the CD and could thereby help to regulate Na⁺ balance and systemic BP.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673