activation of purinergic receptors and physiological responses such a spreading cytoplasmic waves of calcium. Moreover, this could be responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to larger molecules. Clinical significance Inflammation On T cells activation of P2X7 receptors can activate the T cells or cause T cell differentiation, can affect T cell migration or (at high extracellular levels of ATP and/or NAD+) can induce cell death. The CD38 enzyme on B lymphocytes and macrophages reduces extracellular NAD+, promoting the survival of T cells. Neuropathic pain Microglial P2X7 receptors are thought to be involved in neuropathic pain because blockade or deletion of P2X7 receptors results in decreased responses to pain, as demonstrated in vivo. Moreover, P2X7 receptor signaling increases the release of proinflammatory molecules such as IL-1β, IL-6, and TNF-α. In addition, P2X7 receptors have been linked to increases in proinflammatory cytokines such as CXCL2 and CCL3. P2X7 receptors are also linked to P2X4 receptors, which are also associated with neuropathic pain mediated by microglia. Osteoporosis Mutations in this gene have been associated to low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women. Diabetes The ATP/P2X7R pathway may trigger T-cell attacks on the pancreas, rendering it unable to produce insulin. This autoimmune response may be an early mechanism by which the onset of diabetes is caused. Research Possible link to hepatic fibrosis One study in mice showed that blockade of P2X7 receptors attenuates onset of liver fibrosis. See also Purinergic receptor P2X receptor References Further reading External links Ion channels