J774 mouse macrophages express an ionotropic receptor gated by extracellular ATP. Activation of this receptor, currently named purinergic P2Z, causes transmembrane ion fluxes, plasma membrane depolarization, cell swelling and eventual cell death. The physiological role of this receptor is as yet unknown. In the present report we show that macrophage cell clones that hypo-express the P2Z receptor showed a very low degree of spontaneous cell death in culture, while hyper-expressing clones were exceedingly susceptible to cell death. To further support a role for ATP receptors in spontaneous cell death, addition to the macrophage cell cultures of oxidized ATP, a selective inhibitor of ionotropic purinergic receptors, or the ATP-hydrolysing enzyme apyrase, also reduced spontaneous death
