Activation of P2X7R mediates both peroxynitrite- and Hsp90NY-triggered PC12 cell death. PC12 cell were incubated for 1 h with the P2X7R inhibitors KN-62 (1 μM) and BBG (10 μM), and the intracellular calcium chelator BAPTA.AM (1 μM; BAPTA) followed by treatment with peroxynitrite (A), or Hsp90NY was intracellularly released using Chariot (B), followed by incubation with the inhibitors for additional 24 h before assessing cell viability. For the down-regulation experiments, cells were transduced with a shRNA to P2X7R (shRNA P2X7R) or a scrambled sequence (shRNA CTR) 24 h before treatment with peroxynitrite, and cell viability assessed after additional 24 h. The values represent the mean ± SD (n = 3–5 with 3–8 replicates). *p < 0.001 vs control and ** vs ONOO− or Hsp90NY by one-way ANOVA followed by Holm-Sidak's multiple comparison test.