Molecular physiology of p2x receptors and atp signalling at synapses

Abstract

There are two broad classes of ATP receptor in the nervous system: P2X and P2Y receptors. P2X receptors, a group of cation-selective ion channels, are the focus of this review. There are seven different P2X subunits, each of which has two transmembrane domains inserted in the plasma membrane such that both the amino and the carboxyl termini are located intracellularly. The ATP-binding site of P2X receptors seems to be located near the transmembrane domains and is thought to involve several lysine residues. The second transmembrane domain of P2X subunits forms the channel pore, which is permeable to different cations including calcium. Although their exact subunit stochiometry is controversial, most of the evidence supports the idea that P2X receptors assemble as trimers. P2X receptors are ubiquitously expressed in the nervous system. Indeed, they are present both pre- and postsynaptically. Activation of presynaptic P2X receptors can modulate release of several neurotransmitters at a variety of synapses. Postsynaptically, ATP can elicit excitatory synaptic currents in some cells, but they seem to contribute to a small part of the total excitatory drive. P2X receptors have been implicated in processing pain information. ATP released from damaged tissue can act directly on P2X receptors present in the primary sensory afferent. In turn, the terminals of sensory neurons release ATP onto dorsal horn cells. In addition, presynaptic receptors on the terminals of the sensory neuron facilitate the release of glutamate onto dorsal horn cells, and presynaptic P2X receptors on inhibitory nerve terminals also facilitate the release of GABA and glycine. The balance between inhibitory and excitatory effects contributes to the spinal processing of painful information.