Figure 2.
Histone-evoked P2XR7 currents are inhibited by non-selective P2XR antagonists, but not inhibited by selective P2XR7 antagonists. (A) Representative trace of current versus time recorded from a Xenopus oocyte 24–48 h after nuclear injection of plasmid cDNA encoding mouse P2XR7. 5 μM Suramin inhibits ATP- and histone-evoked currents. (B) Average current after 30 s of antagonist treatment relative to baseline histone-evoked current (Ctrl, 30 s time/vehicle control; 5 μM PPADS, 10 μM TNP-ATP, 5 μM Suramin, Ave ± SEM, n = 3–4 animals, 7–18 cells, P values from ANOVA with multiple comparisons are reported in the figure). (C–H) Representative trace and average ATP-evoked current after application of indicated P2XR7-selective antagonists on ATP-activated, open, channels. (D) 10 μM AZ10606120 (AZ10, Ave ± SEM, n = 3 animals, 18 cells). (E) 10 μM A438079 (A43, Ave ± SEM, n = 2 animal, 8 cells). (F) 50 μM GW791343 (GW, Ave ± SEM, n = 5 animals, 16 cells). (G) 10 μM AZ11645373 (AZ11, Ave ± SEM, n = 3 animals, 8 cells). (H) 1 μM KN-62 (KN62, Ave ± SEM, n = 2 animals, 7 cells). P values by Student’s t test indicated above each graph. (I–N) Representative trace and average histone-evoked current after application of indicated P2XR7-selective antagonist on histone-activated, open, channels. (J) 10 μM AZ10606120 (AZ10, Ave ± SEM, n = 3 animals, 10 cells). (K) 10 μM A438079 (A43, Ave ± SEM, n = 2 animals, 8 cells). (L) 50 μM GW791343 (GW, Ave ± SEM, n = 2 animals, 9 cells). (M) 10 μM AZ11645373 (AZ11, Ave ± SEM, n = 3 animals, 8 cells). (N) 1 μM KN-62 (KN62, Ave ± SEM, n = 1 animal, 3 cells). P values by Student’s t test indicated above each graph. (O–Q) Representative trace (O) and average ATP- and histone-evoked currents before (control) and after pre-application of P2XR7-selective antagonists. (P) ATP-evoked currents (Ave ± SEM) after pre-application of AZ10 (n = 2 animals, 9 cells), A43 (n = 2 animals, 8 cells), GW (n = 3 animals, 9 cells), AZ11 (n = 3 animals, 9 cells), or KN62 (n = 2 animals, 7 cells). (Q) Histone-evoked currents (Ave ± SEM) after pre-application of AZ10 (n = 3 animals, 15 cells), A43 (n = 3 animals, 11 cells), GW (n = 2 animals, 9 cells), AZ11 (n = 2 animals, 7 cells), or KN62 (n = 2 animals, 9 cells). P values by one-way ANOVA (non-parametric) indicated above the graph.

Histone-evoked P2XR7 currents are inhibited by non-selective P2XR antagonists, but not inhibited by selective P2XR7 antagonists. (A) Representative trace of current versus time recorded from a Xenopus oocyte 24–48 h after nuclear injection of plasmid cDNA encoding mouse P2XR7. 5 μM Suramin inhibits ATP- and histone-evoked currents. (B) Average current after 30 s of antagonist treatment relative to baseline histone-evoked current (Ctrl, 30 s time/vehicle control; 5 μM PPADS, 10 μM TNP-ATP, 5 μM Suramin, Ave ± SEM, n = 3–4 animals, 7–18 cells, P values from ANOVA with multiple comparisons are reported in the figure). (C–H) Representative trace and average ATP-evoked current after application of indicated P2XR7-selective antagonists on ATP-activated, open, channels. (D) 10 μM AZ10606120 (AZ10, Ave ± SEM, n = 3 animals, 18 cells). (E) 10 μM A438079 (A43, Ave ± SEM, n = 2 animal, 8 cells). (F) 50 μM GW791343 (GW, Ave ± SEM, n = 5 animals, 16 cells). (G) 10 μM AZ11645373 (AZ11, Ave ± SEM, n = 3 animals, 8 cells). (H) 1 μM KN-62 (KN62, Ave ± SEM, n = 2 animals, 7 cells). P values by Student’s t test indicated above each graph. (I–N) Representative trace and average histone-evoked current after application of indicated P2XR7-selective antagonist on histone-activated, open, channels. (J) 10 μM AZ10606120 (AZ10, Ave ± SEM, n = 3 animals, 10 cells). (K) 10 μM A438079 (A43, Ave ± SEM, n = 2 animals, 8 cells). (L) 50 μM GW791343 (GW, Ave ± SEM, n = 2 animals, 9 cells). (M) 10 μM AZ11645373 (AZ11, Ave ± SEM, n = 3 animals, 8 cells). (N) 1 μM KN-62 (KN62, Ave ± SEM, n = 1 animal, 3 cells). P values by Student’s t test indicated above each graph. (O–Q) Representative trace (O) and average ATP- and histone-evoked currents before (control) and after pre-application of P2XR7-selective antagonists. (P) ATP-evoked currents (Ave ± SEM) after pre-application of AZ10 (n = 2 animals, 9 cells), A43 (n = 2 animals, 8 cells), GW (n = 3 animals, 9 cells), AZ11 (n = 3 animals, 9 cells), or KN62 (n = 2 animals, 7 cells). (Q) Histone-evoked currents (Ave ± SEM) after pre-application of AZ10 (n = 3 animals, 15 cells), A43 (n = 3 animals, 11 cells), GW (n = 2 animals, 9 cells), AZ11 (n = 2 animals, 7 cells), or KN62 (n = 2 animals, 9 cells). P values by one-way ANOVA (non-parametric) indicated above the graph.

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