Cooperativity between extracellular adenosine 5'-triphosphate and activation of N-methyl-D-aspartate receptors in long-term potentiation induction in hippocampal CA1 neurons.
The mechanism of ATP-induced long-term potentiation (LTP) was studied pharmacologically using guinea-pig hippocampal slices. LTP, induced in CA1 neurons by 10 min application of 10 microM ATP, was blocked by co-application of the N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (5 or 50 microM). In ATP-induced LTP, the delivery of test synaptic inputs (once every 20 s) to CA1 neurons could be replaced by co-application of NMDA (100 nM) during ATP perfusion. These results suggest that, in CA1 neurons, a co-operative effect between extracellular ATP and activation of NMDA receptors is required to trigger the process involved in ATP-induced LTP. In addition, ATP-induced LTP was blocked by co-application of an ecto-protein kinase inhibitor, K-252b (40 or 200 nM), whereas a P2X purinoceptor antagonist, pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid 4-sodium (50 microM), or a P2Y purinoceptor antagonist, basilen blue (10 microM), had no effect.The results of the present study, therefore, indicate that the mechanisms of ATP-induced LTP involve the modulation of NMDA receptors/Ca(2+) channels and the phosphorylation of extracellular domains of synaptic membrane proteins, one of which could be the NMDA receptor/Ca(2+) channel.
Fujii
S
S
Department of Physiology,Yamagata University School of Medicine,Yamagata 990-9585, Japan. sfujii@med.id.yamagata-u.ac.jp
Kato
H
H
Kuroda
Y
Y
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D026121:Indole Alkaloids; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D026121:Indole Alkaloids; D058919:Purinergic P2 Receptor Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D015763:2-Amino-5-phosphonovalerate; D000255:Adenosine Triphosphate; C049985:staurosporine aglycone; D011493:Protein Kinase C