抄録
Extracellular ATP elicits a variety of physiological activities through the activation of ionotropic P2X and metabotropic P2Y receptors. Recent findings have indicated that spinal cord injury is associated with prolonged purinergic receptor activation, which results in excitotoxicity of spinal motoneurons. However, it is unknown whether purinergic receptor activation can modulate synaptic transmission in spinal motoneurons. By use of the whole-cell patch-clamp technique, we investigated the effects of extracellular ATP on motoneurons of rat spinal cord slices. Bath application of ATP or ATPγS, a metabolically stable ATP analog, produced an inward current at a holding potential of -70 mV in about 30% of neurons examined. When applied repeatedly at a time interval of 10 min, ATPγS produced similar responses with almost the same amplitude. In the presence of TTX, ATPγS also induced an inward current without any significant decrease in amplitude. The ATPγS-induced inward current was mimicked by 2-methylthio ADP, an agonist for P2Y1, P2Y12, and P2Y13 receptors, but not by α,β-methylene ATP, BzATP, UTP, or UDP. The ATPγS-induced inward current was significantly suppressed by PPADS, a purinergic receptor antagonist, or MRS2179, a selective P2Y1 receptor antagonist. These results indicate that extracellular ATP directly excites a subpopulation of spinal motoneurons by the activation of P2Y1receptors. Thus, P2Y1 receptor antagonists may constitute a new medication for the treatment of spinal cord injury. [J Physiol Sci. 2007;57 Suppl:S148]
