Extracellular adenosine 5'-triphosphate-evoked glutamate release in cultured hippocampal neurons.
Characteristics of extracellular ATP-evoked electrical responses in rat hippocampal neurons were investigated. Extracellular ATP (100 microM) induced a rapid depolarization followed by repetitive firings of spikes in these cells under whole-cell current-clamp. In whole-cell voltage-clamp experiments, ATP activated 2 types of inward currents that were inhibited by P2-purinoceptor blocker suramin (300 microM). One is a small (about -20 pA) sustained current which is insensitive to tetrodotoxin (TTX), and the other is a large (-100 to -300 pA) transient current which abolished in the presence of 3 microM TTX. The ATP-induced transient current was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 30 microM), a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist. ATP failed to induce the transient current in the cell which showed the desensitization to quisqualic acid (QA; 10 microM), a non-NMDA receptor agonist. These findings suggest that ATP directly activates small sustained currents, and indirectly induces the transient currents by evoking glutamate release.
Inoue
K
K
Division of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
Nakazawa
K
K
Fujimori
K
K
Watano
T
T
Takanaka
A
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D005333:Fetus; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D005971:Glutamates; D011810:Quinoxalines; D018698:Glutamic Acid; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000255:Adenosine Triphosphate; D016318:Quisqualic Acid; D007608:Kainic Acid