Features of P2X receptor-mediated synapses in the rat brain: why doesn't ATP kill the postsynaptic cell?

In addition to the widespread excitatory transmission mediated by glutamate receptors, P2X receptors also mediate fast excitatory synaptic transmission in the brain. The receptors in the brain have some features which are different from the more extensively characterized peripheral P2X receptors, possibly suggesting a difference in the subunits making up the protein. Perhaps the most notable feature of the central receptors is a higher Ca2+ permeability than seen in other areas, with a linear current voltage relation. The potential danger to the postsynaptic cell of the high Ca2+ permeability of neuronal P2X receptors is discussed and various forms of inbuilt features of the synapse and receptors are outlined which would combine to protect the neurons from excessive Ca2+ influx and consequent danger of cell death. These features include a rapid breakdown of transmitter in the cleft, which not only removes the ATP from the cleft quickly, but also results in the production of adenosine. Evidence for the interaction of ATP-mediated transmission and stimulation of purinoceptors by this adenosine is presented from experiments using patch-clamp recording in brain slices. This demonstrates an elegant negative feedback mechanism by which a fast excitatory transmitter can be inactivated by breakdown to a product which acts as a slow inhibitory modulator, controlling release of the original transmitter.