抄録
An increase of extracellular ATP concentration is observed during brain ischemia, but the origin of released ATP is not well understood. We investigated the mechanisms of ATP release from rat hippocampal slice cultures under ischemic conditions. When slice cultures were subjected to oxygen-glucose deprivation (OGD), significant release of ATP was observed within 10 min. OGD-induced ATP release was almost completely prevented by pretreatment with tetanus toxin (TeTX) and was largely suppressed by the removal of extracellular Ca2+ or by the application of TTX or an NMDA receptor antagonist, MK-801, whereas it was slightly diminished by Gd3+, a blocker of maxi-anion channels which are known to mediate glial ATP release. Slice cultures also responded to glutamate exposure for over 10 min with gradual release of ATP. Glutamate-induced ATP release was partially sensitive to TeTX and was markedly suppressed by combined application of MK-801 and a non-NMDA receptor antagonist, CNQX. Neuron-depleted slice cultures responded to glutamate exposure, but not to OGD, with ATP release. Glutamate-induced ATP release from neuron-depleted slices was little sensitive to TeTX but was significantly suppressed by Gd3+. Taken together, it is suggested that ischemic insult-induced ATP release from slice cultures comprises two components: one is the rapid release caused by exocytosis of neuronal synaptic vesicles containing ATP and glutamate, and another is the glutamate-dependent gradual release via Gd3+-sensitive glial pathways, presumably maxi-anion channels. [J Physiol Sci. 2007;57 Suppl:S126]
