Abstract
Recent findings have indicated that a secondary neuronal damage following spinal cord injury is associated with prolonged purinergic receptor activation, which results in excitotoxicity of spinal motoneurons. In this study, we investigated the effects of extracellular ATP on lamina IX neurons of rat spinal cord slices by using the whole-cell patch-clamp technique. At a holding potential of -70 mV, ATPγS, a nonhydrolyzable ATP analog, generated an inward current, which was resistant to tetrodotoxin, in about a half of the lamina IX neurons tested. The ATPγS-induced inward current was not reproduced by α,β-methylene ATP, BzATP, UTP, or UDP, but mimicked by 2-methylthio ADP. The ATPγS-induced inward current was suppressed by the addition of GDPβS into patch-pipette solution, thus suggesting that metabotropic P2Y receptors were activated by ATPγS. The ATPγS-induced inward current was often accompanied by a significant increase in the frequency of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs). α,β-Methylene ATP did not change any holding currents, but instead increased sEPSC frequency in a subpopulation of lamina IX neurons. PPADS inhibited both the inward current and the increase in sEPSC frequency by ATPγS. On the other hand, MRS2179 blocked the ATPγS-induced inward current, but did not affect the ATPγS-induced increase in sEPSC frequency. These results indicate that extracellular ATP facilitates excitatory synaptic transmission by activating both P2X and P2Y receptors in a subpopulation of spinal motoneurons. [J Physiol Sci. 2008;58 Suppl:S132]
