Proapoptotic plasma membrane pore: P2X7 receptor

ATP is not only the universal currency of energy metabolism but also a ubiquitous extracellular messenger. Among its many effects the ability to trigger cell death has attracted considerable interest. The plasma membrane receptor responsible for this effect has been cloned and shown to belong to the P2X family (P2X7). The P2X7 receptor is a plasma membrane ion channel that, under certain conditions, can grow to form a nonselective pore. Prolonged opening of this receptor is a potent apoptotic stimulus for several cell types. The main mechanism responsible for this deadly effect seems to reside in the drastic upset of the intracellular concentration of Ca2+ as well as K+. The loss of intracellular K+ has a permissive effect on the progression of apoptosis by causing the activation of key proapoptotic enzymes such as caspase 3 and NUC18. The P2X7 receptor could be an interesting model for the study of apoptotic pathways triggered by plasma membrane channels. © 2001 Wiley-Liss, Inc.