P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb

de Bruijn, P. I. A., Bleich, Markus, Praetorius, H. A. and Leipziger, J. (2015) P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb Acta Physiologica, 213 (1). pp. 277-284.

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Abstract

AimsExtracellular ATP is an important regulator of renal tubular transport. Recently, we found that basolateral ATP markedly inhibits Na+ andCl(-) absorption in mouse medullary thick ascending limb (mTAL) viaa P2X receptor. The underlying mechanism that mediates this ATP-dependent transport inhibition in mTAL is, however, unclear. The renal outer medullary K+ channel (ROMK) is sensitive to intracellular pH where a reduction leads to closing of ROMK. We speculated that P2X receptor stimulation in the TAL could lead to changes in pH(i), leading to a reduction in NaCl transport. MethodsTo test this hypothesis, we measured pH(i) in single perfusedmouse mTALs using the fluorescent ratiometric dye 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethylester. ResultsInterestingly, basolateral ATP (100m) caused a prominent, reversible intracellular alkalization of mTAL, with an average pH(i) increase of 0.140.02 (n=14). This was completely abolished by the P2X receptor antagonist periodate-oxidized ATP (50m). The P2X receptor-mediated intracellular alkalization required the activity of the apical Na+/H+ exchanger (NHE3). Typically, G(q)-coupled receptors cause a significant acidification of tubular epithelial cells, which was confirmed in this study, by P2Y(2) and Ca2+ sensing receptor stimulation. ConclusionThis study reports that stimulation of basolateral P2X receptors causes a substantial intracellular alkalization in the isolated perfused mouse mTAL. This intracellular alkalization is mediated through an increased apical NHE3 activity, similar to what we previously observed when tubular transport is inhibited with furosemide. This increased NHE3 activity causes H+ secretion in the mTAL and provides further support that the TAL is a site of urinary acidification.

Document Type: Article
Additional Information: Times Cited: 0
Research affiliation: Kiel University
Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
ISSN: 1748-1708
Projects: Future Ocean
Date Deposited: 20 Oct 2016 10:56
Last Modified: 20 Oct 2016 10:56
URI: http://eprints.uni-kiel.de/id/eprint/32444

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