P2X receptors in peripheral neurons

Abstract

P2X receptors are a family of ligand-gated ion channels, activated by extracellular ATP. The seven subunits cloned (P2X 1–7) can assemble to form homomeric and heteromeric receptors. Peripheral neurons of neural crest origin (e.g. those in dorsal root, trigeminal, sympathetic and enteric ganglia) and placodal origin (e.g. those in nodose and petrosal ganglia) express mRNAs for multiple P2X subunits. In this review, we summarize the molecular biological, electrophysiological and immunohistochemical evidence for P2X receptor subunits in sensory, sympathetic, parasympathetic, pelvic and myenteric neurons and adrenomedullary chromaffin cells. We consider the pharmacological properties of these native P2X receptors and their physiological roles. The responses of peripheral neurons to ATP show considerable heterogeneity between cells in the same ganglia, between ganglia and between species. Nevertheless, these responses can all be accounted for by the presence of P2X 2 and P2X 3 subunits, giving rise to varying proportions of homomeric and heteromeric receptors. While dorsal root ganglion neurons express predominantly P2X 3 and rat sympathetic neurons express mainly P2X 2 receptors, nodose and guinea-pig sympathetic neurons express mixed populations of P2X 2 and heteromeric P2X 2/3 receptors. P2X receptors are important for synaptic transmission in enteric ganglia, although their roles in sympathetic and parasympathetic ganglia are less clear. Their presence on sensory neurons is essential for some processes including detection of filling of the urinary bladder. The regulation of P2X receptor expression in development and in pathological conditions, along with the interactions between purinergic and other signalling systems, may reveal further physiological roles for P2X receptors in autonomic and sensory ganglia.