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Changes in tubular fluid pH and nucleotide concentration alter P2 receptor‐mediated regulation of renal ENaC
Author(s) -
Wildman Scott S.P.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.602.5
Subject(s) - epithelial sodium channel , receptor , reabsorption , amiloride , chemistry , medicine , apical membrane , p2y receptor , patch clamp , endocrinology , kidney , biophysics , biology , sodium , biochemistry , purinergic receptor , membrane , organic chemistry
Epithelial Na channels (ENaC) control Na reabsorption along the renal collecting duct (CD) and help determine systemic BP. We have shown that ENaC activity is inhibited by activation of apical P2Y 2 and/or 4 receptors and P2X 4 and/or 4/6 receptors when luminal concentrations of Na are high, and that apical P2X 4 and/or 4/6 receptors switch to being potentiators of ENaC activity when concentrations of Na are lowered. Here we address the effect of altering luminal pH, and concentration of P2 receptor (P2R) agonists, on P2R‐mediated regulation of ENaC in the CD. Rats were maintained on a low Na diet to increase ENaC expression. Kidneys were microdissected, and CD split‐open to expose the apical membrane of cells for patch clamp experiments. When concentrations of P2R agonists were high, UTP‐evoked currents ( i.e. P2Y 2 and/or 4 ‐mediated) reduced, and 2meSATP‐evoked currents ( i.e. P2X 4 and/or 4/6 ‐mediated) increased, the amplitude of subsequent ENaC‐mediated currents. Lowering pH from 7.4 to 6.5 did not alter these effects. Further acidification to pH 5.5 increased the degree of inhibition by UTP and abolished the effects of 2meSATP‐evoked currents. At pH 7.4 and 6.5, when concentrations of P2R agonists were lowered, the inhibitory effect of UTP was abolished and the potentiating effect of 2meSATP was unaltered. Apical P2R and ENaC interactions in CD are complex and dependent on luminal Na and nucleotide concentration, and pH.