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Basolateral P2X4-like receptors regulate the extracellular ATP-stimulated epithelial Na+ channel activity in renal epithelia

Lookup NU author(s): Professor Chris Edwards


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Extracellular ATP initiates potent effects on sodium transport across renal epithelia through membrane-associated purinergic receptors. Dependent on the location of these receptors, ATP either inhibits or stimulates sodium reabsorption. Using A6 cells, transepithelial electrical resistance measurements, and scanning ion conductance microscopy, we have identified the purinergic receptors involved in the stimulatory action on the epithelial cell basolateral plasma membrane. Addition of the potent P2X4 receptor agonist 2-methylthio-ATP (2MeSATP) to the basolateral side of the A6 monolayer stimulated amiloride-sensitive sodium conductance and produced similar cell morphological changes to those found with ATPγS, aldosterone, or hypotonic stress. The agonist potency order determined by sodium conductance changes of the monolayer was: 2MeSATP ≥ ATPγS > CTP, a similar agonist potency profile to that of cloned P2X4 receptors but with higher sensitivity for β, γ-methylene-ATP and α,β-methylene-ATP. We further demonstrated that the ATP effect on sodium transport was potentiated by ivermectin, not blocked by suramin and PPADS, enhanced by Zn2+ but not by Cu2+, and significantly reduced but not totally inhibited by brilliant blue G. These results led us to conclude that basolateral P2X 4-like receptors were involved. We suggest that there is a reciprocal purinergic system acting both at a basolateral and apical location for control of Na+ transport. This requires a mechanism within the cell that leads to either basolateral or apical ATP release to regulate renal tubular function. Copyright © 2007 the American Physiological Society.

Publication metadata

Author(s): Zhang Y, Sanchez D, Gorelik J, Klenerman D, Lab M, Edwards C, Korchev Y

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology - Renal Physiology

Year: 2007

Volume: 292

Issue: 6

Pages: F1734-F1740

Print publication date: 01/06/2007

ISSN (print): 0363-6127

ISSN (electronic): 1522-1466

Publisher: American Physiological Society


DOI: 10.1152/ajprenal.00382.2006

PubMed id: 17356127


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