Abstract We previously demonstrated that there is a paucity of brush-border membrane NHE3 in neonates, the predominant Na + /H + exchanger in the adult proximal tubule, while NHE8 is relatively highly expressed in neonates compared with adults. We recently showed that metabolic acidosis in neonatal rodents can increase brush-border membrane NHE8 protein expression and Na + /H + exchange activity. To further examine the regulation of NHE8 by acid, we incubated NRK cells, which express NHE8 but not NHE3, with either acid or control media (6.6 vs. 7.4). There was an increase in Na + /H + exchanger activity within 6 h of incubation with acid media assessed as the rate of sodium-dependent recovery of pH from an acid load (dpH i /d t ). The acid stimulation persisted for at least 24 h. The increase in Na + /H + exchange activity was paralleled by an increase in surface expression of NHE8, assessed by surface biotinylation and streptavidin precipitation. The increase in both apical membrane NHE8 protein expression and Na + /H + exchange activity with pH 6.6 media compared with 7.4 media was not affected by actinomycin D or cycloheximide consistent with an increase in surface expression independent of mRNA or protein synthesis. Furthermore, there was no increase in total cellular NHE8 protein abundance or mRNA abundance with acid media. Finally, we demonstrate that the increase in surface expression of NHE8 with acid media was blocked by colchicine and cytochalasin D and mediated by acid increasing the rate of exocytosis. In conclusion, NHE8 surface expression and activity are regulated by acid media by increasing the rate of trafficking to the apical membrane. proximal tubule acidification neonate Na + /H + exchange Copyright © 2012 the American Physiological Society « Previous Table of Contents This Article Published online before print November 2011 , doi: 10.​1152/​ajprenal.​00331.​2011 AJP - Renal Physiol February 2012 vol. 302 no. 4 F495-F503 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajprenal.00331.2011v1 302/4/F495 most recent Classifications Article Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Joseph, C. Articles by Baum, M. PubMed PubMed citation Articles by Joseph, C. Articles by Baum, M. Related Content Load related web page information Current Issue February 2012, 302 (4) Alert me to new issues of AJP - Renal Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6127 Online ISSN: 1522-1466 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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