P2X receptors and synaptic plasticity

Adenosine triphosphate (ATP) is released in many synapses in the CNS either together with other neurotransmitters, such as glutamate and GABA, or on its own. Postsynaptic action of ATP is mediated through metabotropic P2Y and ionotropic P2X receptors abundantly expressed in neural cells. Activation of P2X receptors induces fast excitatory postsynaptic currents in synapses located in various brain regions, including medial habenula, hippocampus and cortex. P2X receptors display relatively high Ca2+ permeability and can mediate substantial Ca2+ influx at resting membrane potential. P2X receptors can dynamically interact with other neurotransmitter receptors, including N-methyl-D-aspartate (NMDA) receptors, GABA(A) receptors and nicotinic acetylcholine (ACh) receptors. Activation of P2X receptors has multiple modulatory effects on synaptic plasticity, either inhibiting or facilitating the long-term changes of synaptic strength depending on physiological context. At the same time precise mechanisms of P2X-dependent regulation of synaptic plasticity remain elusive. Further understanding of the role of P2X receptors in regulation of synaptic transmission in the CNS requires dissection of P2X-mediated effects on pre-synaptic terminals, postsynaptic membrane and glial cells.