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Differential regulation of renal ENaC by apical P2X and P2Y receptors
Author(s) -
Wildman Scott Shaw Peppiatt,
Turner Clare M,
Marks Joanne,
Shirley David G,
King Brian F,
Unwin Robert J
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.21.6.a1328-a
ENaC activity is inhibited by P2 receptors (P2Rs) activated by extracellular nucleotides in the renal collecting duct (CD). However, controversy exists over the mechanism of inhibition, the P2R subtype(s) involved and molecular pathway(s) activated. This study has addressed the relationship between apical P2Rs and ENaC inhibition in the rat CD. Immunohistochemistry demonstrated apical co‐localsation of P2X 1 , 4 and 6 subunits and P2Y 2 , 4 and 11 receptors with ENaC subunits in principal cells of Na + ‐restricted rats. Apically‐applied ATP, ATPγS, Ap 6 A, UTP, 2meSATP and BzATP all elicited inward currents ( 600 pA; 10 μM) in principal cells of split‐open CDs from Na + ‐restricted rats, using whole‐cell patch clamp techniques ( V h = −60 mV). ATP‐ (P2X/P2Y agonist), UTP‐ (P2Y 2 /P2Y 4 /P2Y 11 agonist), 2meSATP (P2X/P2Y 2 agonist) ‐ and ATPγS‐ (P2X agonist) evoked currents reduced the amplitude of subsequent ENaC‐mediated ( I am‐s ) current‐voltage relationships, without changing the inward rectification or reversal potential. Lowering extracellular Na + concentration from 145 to 100 mM did not alter the degree of inhibition caused by UTP‐evoked currents, but surprisingly 2meSATP‐ or ATPγS‐evoked currents potentiated the amplitude of I am‐s current‐voltage relationships. These data suggest the ENaC activity is inhibited by apical P2Y 4 and P2X 4 , 1/4 and/or 4/6 receptors when extracellular Na + concentrations are high (145 mM) but apical P2X 4, 1/4 and/or 4/6 receptors switch to being stimulators of ENaC activity when extracellular Na + is lowered (to 100 mM). Supported by the British Heart Foundation