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- Title
Dietary Na<sup>+</sup> inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y<sub>2</sub>-receptor tone.
- Authors
Pochynyuk, Oleh; Rieg, Timo; Bugaj, Vladislav; Schroth, Jana; Fridman, Alla; Boss, Gerry R.; Insel, Paul A.; Stockand, James D.; Vallon, Volker
- Abstract
Apical release of ATP and UTP can activate P2Y2 receptors in the aldosterone-sensitive distal nephron (ASDN) and inhibit the open probability (Po) 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 Po, 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 P2Y2 receptors in mice (P2Y2-/-; littermates to wild-type mice) or inhibition of apical P2Yreceptor activation in wild-type mice prevents dietary Na+-induced lowering of ENaC Po. Although they lack suppression of ENaC Po by dietary NaCl, P2Y2-/- 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 P2Y2-/- mice. The studies indicate a key role of the apical ATP/UTP-P2Y2-receptor system in the inhibition of ENaC Po in the ASDN in response to an increase in Na+ intake, thereby contributing to NaCl homeostasis and blood pressure regulation.
- Subjects
SODIUM channels; ADENOSINE triphosphate; ALDOSTERONE; BLOOD pressure; NUCLEOTIDES
- Publication
FASEB Journal, 2010, Vol 24, Issue 6, p2056
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.09-151506