P2X receptors as cell-surface ATP sensors in health and disease

P2X receptors are membrane ion channels activated by the binding of extracellular adenosine triphosphate (ATP). For years their functional significance was consigned to distant regions of the autonomic nervous system, but recent work indicates several further key roles, such as afferent signalling, chronic pain, and in autocrine loops of endothelial and epithelial cells. P2X receptors have a molecular architecture distinct from other ion channel protein families, and have several unique functional properties. ATP the outsider ATP is the ubiquitous currency for energy transfer inside all living cells, but it is also found in the extracellular space, where it can interact with transmembrane receptors to influence intracellular events in nerve cells, muscles, glands and immune cells. On release from a cell, ATP can activate P2X receptors, non-selective cation channels found in most tissues of the body. A lack of pharmacological tools has resulted in a poor understanding of the physiological roles that these receptors play. But with P2X blockers such as suramin and PPADS now available, the importance of these receptors as cell-surface ATP sensors in health and disease is becoming clear.