P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2 X 7 , have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in a channel pore permeable to molecules as large as 900 daltons. The P2 X 7 receptor was originally described in cells of hematopoietic origin, and mediates the influx of C a 2 + and N a + and C a 2 + and N a + ions as well as the release of proinflammatory cytokines. P2 X 7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1 𝛽 , a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2 X 7 , a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2 X 7 receptors provides an inflammatory stimulus, and P2 X 7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2 X 7 receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. Apoptotic cell death occurs in a number of vascular diseases, including atherosclerosis, restenosis, and hypertension, and may be linked to the release of ATP from endothelial cells, P2 X 7 receptor activation, proinflammatory cytokine production, and endothelial cell apoptosis. In this context, the P2 X 7 receptor may be viewed as a gateway of communication between the nervous, immune, and cardiovascular systems.