Abstract: AIM: To investigate the sensitivity of P2X7 receptor to its specific agonist B_ZATP and the effect of propofol on P2X7-gated currents in RAW264.7 macrophages under different extracellular pH values. METHODS: RAW264.7 cells were cultured, and whole-cell patch clamp technique was used. B_ZATP (10-10000 μmol/L) was applied for 5 seconds, the currents were recorded, and the EC₅₀ value of B_ZATP was achieved under the extracellular pH value of 7.4 or 6.0. Propofol (1-100 μmol/L) was applied to the cells for 1 min, then B_ZATP with two times EC₅₀ value was applied, the IC₅₀ or EC₅₀ value of propofol was achieved under different extracellular pH values. To investigate the effect of propofol on the dose-response curve of B_ZATP under different extracellular pH values, propofol with IC₅₀ value was applied, and B_ZATP (10-10000 μmol/L) was applied for 5 seconds, the EC₅₀ value of B_ZATP was achieved. RESULTS: B_ZATP could induce the inward currents in a dose-dependent manner, and the EC₅₀ value of B_ZATP was (112±26) μmol/L and (643±87) μmol/L at extracellular pH value of 7.4 or 6.0. Propofol could inhibit P2X7-gated currents at pH 7.4, and the IC₅₀ value was (31±6) μmol/L; but propofol increased P2X7-gated currents at pH 6.0, and the EC₅₀ value was (38±6) μmol/L. The IC₅₀ value of propofol made the dose-response curve of B_ZATP shifted rightward at pH 7.4, or leftward at pH 6.0. CONCLUSION: The sensitivity of P2X7 receptor to B_ZATP decreases when extracellular pH value changes from 7.4 to 6.0. Propofol with clinically related concentrations could inhibit P2X7-gated currents at pH 7.4, and increase P2X7-gated currents at pH 6.0 extracellularly.

Key words: Propofol, P2X7 receptor, Macrophage, Extracellular pH value