The Role of Extracellular ATP in Hippocampal Long-Term Potentiation

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  • Fujii Satoshi
    Department of Physiology, Yamagata University School of Medicine

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  • ATP- and Adenosine-Mediated Signaling in the Central Nervous System: The Role of Extracellular ATP in Hippocampal Long-Term Potentiation
  • Role of Extracellular ATP in Hippocampal Long Term Potentiation

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Application of 10 μM ATP for 10 min transiently depressed, then slowly augmented, synaptic transmission in CA1 neurons, leading to long-term potentiation (LTP) (ATP-induced LTP). This ATP-induced LTP was blocked by addition of an N-methyl-<sc>D</sc>-aspartate (NMDA) glutamate receptor antagonist, <sc>D</sc>,<sc>L</sc>-2-amino-5-phosphonovalerate (5 μM). For ATP-induced LTP, delivery of test synaptic inputs once every 20 s to CA1 neurons could be substituted by application of 100 nM NMDA during ATP perfusion. In addition, ATP-induced LTP was blocked by co-application of an ecto-protein kinase inhibitor, K-252b (40 nM), whereas a P2X purinoceptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid 4-sodium (50 μM), or a P2Y purinoceptor antagonist, basilen blue (10 μM), had no effect. These results, therefore, indicate that the mechanisms of ATP-induced LTP involve the modulation of NMDA receptors / Ca2+ channels and the phosphorylation of extracellular domains of synaptic membrane proteins, one of which could be the NMDA receptor / Ca2+ channel.<br>

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