Sodium-Dependent Regulation of Renal Amiloride-Sensitive Currents by Apical P2 Receptors
Wildman, Scott S.P., Marks, Joanne, Turner, Clare M., Yew-Booth, Liang, Peppiatt-Wildman, Claire M., King, Brian F., Shirley, David G., Wang, WenHui and Unwin, Robert J. (2008) Sodium-Dependent Regulation of Renal Amiloride-Sensitive Currents by Apical P2 Receptors. Journal of the American Society of Nephrology, 19 (4). pp. 731-742. ISSN 1046-6673
Abstract
The epithelial sodium channel (ENaC) plays a major role in the regulation of sodium balance and BP by controlling Na+ reabsorption along the renal distal tubule and collecting duct (CD). ENaC activity is affected by extracellular nucleotides acting on P2 receptors (P2R); however, there remain uncertainties over the P2R subtype(s) involved, the molecular mechanism(s) responsible, and their physiologic role. This study investigated the relationship between apical P2R and ENaC activity by assessing the effects of P2R agonists on amiloride-sensitive current in the rat CD. Using whole-cell patch clamp of principal cells of split-open CD from Na+-restricted rats, in combination with immunohistochemistry and real-time PCR, we found that activation of metabotropic P2R (most likely the P2Y2 and/or 4 subtype), via phospholipase C, inhibited ENaC activity. In addition, activation of ionotropic P2R (most likely the P2X4 and/or 4/6 subtype), via phosphatidylinositol-3 kinase, either inhibited or potentiated ENaC activity, depending on the extracellular Na+ concentration; therefore, it is proposed that P2X4 and/or 4/6 receptors might function as apical Na+ sensors responsible for local regulation of ENaC activity in the CD and could thereby help to regulate Na+ balance and systemic BP.
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