| Co-Investigator(Kenkyū-buntansha) |
MICHIKAWA Takayuki The University of Tokyo, Inst, Medical Science, Research Associate, 医科学研究所, 助手 (90282516)
INOUE Takafumi The University of Tokyo, Inst.Medical Science, Research Associate, 医科学研究所, 助手 (10262081)
FURUICHI Teiichi The University of Tokyo, Inst.Medical Science, Associate Prof., 医科学研究所, 助教授 (50219094)
RODOLFO R.Linas Univ.New York, School of Medicine, Professor, 医学部, 教授
福田 光則 東京大学, 医科学研究所, 学振特別研究員
LINAS Rodolf ニューヨーク大学, 医学部, 教授
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| Budget Amount *help |
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1997: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1996: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Research Abstract |
Presynaptic injection of inositol 1,3,4,5-tetraphosphate, inositol 1,3,4,5,6-pentakisphosphate, or inositol 1,2,3,4,5,6-hexakisphosphate・・・・which we denote here the inositol high-polyphosphate series (IHPS) ・・・・is show to block synapic transmission when injected into the preterminal of the squid giant synapse. This effect is not produced by injection of inositol 1,4,5-trisphosphate. The synaptic block is characterized by a time course in the order of 15-45 min, depending on the injection site in the preterminal fiber ; the fastest block occurs when the injection is made at the terminal release site. Presynaptic voltage clamp during transmitter release demonstrates that IHPS block did not modify the presynaptic inward calcium current. Analysis of synaptic noise at the postsynaptic axon shows that both the evoked and spontaneous transmitter release are blocked b the IHPS.Tetanic stimulation of the presynaptic fiber at frequencies of 100 Hz indicates that block is accompanied by gradual reduction of the postsynaptic responce, demonstraing that the block interferes with visicular fusion rather than with vesicular docking. These results, in combination with the recently demonstrated observation that the IHPS bind the C2B domain in synaptotagmin (Fukuda, M.et al. J.Biol.Chem. 1994), suggest that IHPS elements are involved in vesicle fusion and exocytosis. In additon, a scheme is prpoposed in which synaptotagmin triggers transmitter release directly by promoting the fusion og synaptic vesicles with the presynaptic plasmalemma, in agreement with the very rapid nature of transmitter release in chemical synapses.
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