P2X7 pre-synaptic receptors in adult rat cerebrocortical nerve terminals: a role in ATP-induced glutamate release.

Although growing evidence suggests that extracellular ATP might play roles in the control of astrocyte/neuron crosstalk in the CNS by acting on P2X(7) receptors, it is still unclear whether neuronal functions can be attributed to P2X(7) receptors. In the present paper, we investigate the location, pharmacological profile, and function of P2X(7) receptors on cerebrocortical nerve terminals freshly prepared from adult rats, by measuring glutamate release and calcium accumulation. The preparation chosen (purified synaptosomes) ensures negligible contamination of non-neuronal cells and allows exposure of 'nude' release-regulating pre-synaptic receptors. To confirm the results obtained, we also carried out specific experiments on human embryonic kidney 293 cells which had been stably transfected with rat P2X(7) receptors. Together, our findings suggest that (i) P2X(7) receptors are present in a subpopulation of adult rat cerebrocortical nerve terminals; (ii) P2X(7) receptors are localized on glutamatergic nerve terminals; (iii) P2X(7) receptors play a significant role in ATP-evoked glutamate efflux, which involves Ca(2+)-dependent vesicular release; and (iv) the P2X(7) receptor itself constitutes a significant Ca(2+)-independent mode of exit for glutamate.