Figure 7.

The NO and peroxynitrite donor SIN-1 inhibits the BzATP-induced ion channel functions in human P2X7 receptor (hP2X7R) expressing HEK cells via the cysteine C377 in the C-terminal intracellular loop. (A, B) Depicted are representative current curves of whole-cell patch-clamp measurements. (A, C) In control experiments (ctrl) on human wild-type (WT) P2X7R expressing HEK cells (WT hP2X7-HEK), consecutive application of the P2X7R agonist BzATP (100 µM) induced repetitive ion current stimulations (BzATP1 and 2). (B, C) In the presence of SIN-1 (1 mM), the BzATP-induced ion current was blunted. (C) Similar experiments were performed on HEK cells expressing hP2X7R mutants generated by replacing cysteine 377 or 388 by an alanine (hP2X7_C377A; hP2X7_C388A) in the C-terminal intracellular loop. The BzATP-induced current changes (ΔI_BzATP1, ΔI_BzATP2) were normalized (ΔI_BzATP2/ΔI_BzATP1). (C) All BzATP-induced current changes (ΔI_BzATP) are shown as individual data points, bars represent median, whiskers encompass the 25th to 75th percentile. *p ≤ 0.05, Friedman test followed by the Wilcoxon signed-rank test.