ATP mediates synaptic responses to cause intracellular calcium increase in hippocampal neurons

• Published in: Japanese Journal of Pharmacology 1994, Vol.64 (suppl.1), p.78-78
• Main Authors: Kazuhide Inoue, Ken Nakazawa, Shuichi Koizumi, Akira Takanaka
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Recently it has been reported that ATP mediates fast-neurotransmission in medial habenula and sympathetic ganglia. In the hippocampus, glutamate is thought to be a major excitatory neurotransmitter which has been extensively studied in relation to long-term potentiation and neuronal cell death. These processes have been thought to be dependent on an increase in intracellular Ca^2+ (「Ca」i) through glutamate-receptors. We have already reported that ATP activates two types of inward currents by direct stimulation of the ATP-receptor and presumably by evoking glutamate release in cultured rat hippocampal neurons, and that ATP causes an increase in 「Ca」i in PC12 neuronal cells. These findings suggest the possibility that ATP plays a significant role in synaptic transmission in the hippocampus. Here we demonstrate that ATP acts as a neurotransmitter and stimulates an increase in 「Ca」i in cultured rat hippocampal neurons. In addition to glutamatergic synaptic currents, a second population of spontaneously occuning and miniature synaptic currents were recordec which could be distinguished by their slower decay kinetics. These currents were reversibly blocked by suramin (100μM), reactive blue 2 (RB2,100μM) and α,β-methylene ATP(100μM), all ATP receptor antagonists. An increase of 「Ca」i was observed by the application of ATP(100μM). These responses were also blocked by suramin and RB2. In the light of extensive work in the hippocampus on Ca^2+ -dependent phenomena, these results may be highly significant in terms of hippocampal functions.