FIGURE 7.
P2Y2 receptor activation determines the inhibitory effect of ATP as well as of dietary salt on epithelial sodium channel (ENaC) open probability (Po) in connecting tubule (CNT)/cortical collecting duct (CCD). A: representative continuous current traces from cell-attached patches on principal cells (containing ≥2 ENaCs) before and after application of ATP (100 µM) in CNTs/CCDs harvested from wild-type (WT) and P2Y2−/− mice fed a regular 0.32% Na+ diet. Patches clamped to voltage potential of −60 mV and inward Li+ currents through ENaC are downward. Dashed lines indicate the respective current levels with c denoting the closed state. The summary graph on the right shows that ATP reduced ENaC Po, which was blunted in the absence of P2Y2 receptors. *P < 0.05 vs. wild type (WT). B: an increase in dietary NaCl intake for 1 wk reduced ENaC Po in WT. This effect was absent in P2Y2−/− mice. *P < 0.05 vs. WT. C: inhibition of local ATP signaling [hexokinase (+glucose) to degrade local ATP plus suramin to prevent P2 receptor activation] prevented the regulation of ENaC Po by dietary NaCl intake in cell-attached patches from WT mice. *P < 0.05 vs. WT control. [Modified from Pochynyuk et al. (405), with permission from FASEB; permission conveyed through Copyright Clearance Center, Inc.]