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Dietary Na + inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y 2 ‐receptor tone
Author(s) -
Pochynyuk Oleh,
Rieg Timo,
Bugaj Vladislav,
Schroth Jana,
Fridman Alla,
Boss Gerry R.,
Insel Paul A.,
Stockand James D.,
Vallon Volker
Publication year - 2010
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/fj.09-151506
Subject(s) - epithelial sodium channel , endocrinology , homeostasis , medicine , aldosterone , nephron , chemistry , receptor , p2y receptor , kidney , sodium , biology , biochemistry , purinergic receptor , organic chemistry
Apical release of ATP and UTP can activate P2Y 2 receptors in the aldosterone‐sensitive distal nephron (ASDN) and inhibit the open probability ( P o ) of the epithelial sodium channel (ENaC). Little is known, however, about the regulation and physiological relevance of this system. Patch‐clamp studies in freshly isolated ASDN provide evidence that increased dietary Na + intake in wild‐type mice lowers ENaC P o , consistent with a contribution to Na + homeostasis, and is associated with increased urinary concentrations of UTP and the ATP hydrolytic product, ADP. Genetic deletion of P2Y 2 receptors in mice (P2Y 2 −/− ; litter‐mates to wild‐type mice) or inhibition of apical P2Y‐receptor activation in wild‐type mice prevents dietary Na + ‐induced lowering of ENaC P o . Although they lack suppression of ENaC P o by dietary NaCl, P2Y 2 −/− mice do not exhibit NaCl‐sensitive blood pressure, perhaps as a consequence of compensatory down‐regulation of aldosterone levels. Consistent with this hypothesis, clamping mineralocorticoid activity at high levels unmasks greater ENaC activity and NaCl sensitivity of blood pressure in P2Y 2 −/− mice. The studies indicate a key role of the apical ATP/UTP‐P2Y 2 ‐receptor system in the inhibition of ENaC P o in the ASDN in response to an increase in Na + intake, thereby contributing to NaCl homeostasis and blood pressure regulation.—Pochynyuk, O., Rieg, T., Bugaj, V., Schroth, J., Fridman, A., Boss, G. R., Insel, P. A., Stockand, J. D., Vallon, V. Dietary Na + inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y 2 ‐receptor tone. FASEB J. 24, 2056–2065 (2010). www.fasebj.org