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Activation of the P2X7 receptor leads to a rapid,bidirectional flux of cations, causing broad range of hiological responses including cytotoxicity.However,the mechanism of P2X7-mediated cytotoxicity remains largely unexplored.In our previous study,the lack of P2X7-mediated calcium response under normal conditions was found in P2X7+ hematopoietic cell lines.In this study, the P2X7-mediated cytotoxicity in different type of cells(P2X7-,P2X7+ with calcium response,and P2X7+ without calcium response)was investigated.Our results showed that P2X7 agonists, adenosine 5’-triphosphate(ATP)or 2’+3’-O-(4 benzoylbenzoyl)ATP,dose-dependently reduced the cell viability in all P2X7+ cells tested,including J6-1,LCL,and Namalva cells which are negative for P2X7-mediated calcium response, although these effects were lower than those observed in KG1a cells which has normal P2X7 functions.The cytotoxic effect could be blocked by P2X7antagonists, oxidized ATP and 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine.In addition,extalization of phosphatidylserine could be detected in a time-dependent manner and apoptotic morphological changes Could be observed after the activation of P2X7 receptor in J6-1 cells.Furthermore,P2X7-mediated pore formation could be detected in KG1a and J6-1 cells under low-ionic conditions,but not under low-divalent conditions.These effects could not be observed in P2X7-Ramos cells.These results suggested that P2X7 receptor-mediated cytotoxic effects may occur independent of calcium response.