P2X receptor subtype-specific modulation of excitatory and inhibitory synaptic inputs in the rat brainstem

The role of P2 receptors in synaptic transmission to the rat medial nucleus of the trapezoid body (MNTB) was studied in an in vitro brain slice preparation. Whole-cell patch recordings were made and spontaneous synaptic responses studied under voltage clamp during application of P2X receptor agonists. ATP-gammaS (100 mum) had no effect on holding current, but facilitated spontaneous excitatory postsynaptic current (sEPSC) frequency in 41% of recordings and facilitated spontaneous inhibitory postsynaptic currents (sIPSCs) in 20% of recordings. These were blocked by the P2 receptor antagonist suramin (100 mum). alpha,beta-meATP also facilitated sEPSC and sIPSC frequency, while L-beta,gamma-meATP facilitated only sIPSCs. The sEPSC facilitation by ATPgammaS was blocked by TTX (but did not block facilitation of sIPSCs). sEPSC facilitation was blocked by PPADS (30 mum) and the selective P2X(3) receptor antagonist A-317491 (3 mum), suggesting that modulation of sEPSCs involves P2X(3) receptor subunits. alpha,beta-meATP-facilitated sIPSCs were also recorded in wild-type mouse MNTB neurones, but were absent in the MNTB from P2X(1) receptor-deficient mice demonstrating a functional role for P2X(1) receptors in the CNS.