| Project/Area Number |
09671566
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Yamaguchi University |
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Principal Investigator |
YAMADA Yasue Yamaguchi : University School of Medicine, Assistant, 医学部, 助手 (00166737)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Yoshihiro Yamaguchi : University School of Medicine, Assistant Professor, 医学部, 講師 (90301308)
INUI Makoto Yamaguchi : University School of Medicine, Professor, 医学部, 教授 (70223237)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Nicotinic acetylcholine receptor / Neuromuscular junction / Acetylcholine / Succinylcholine / Muscle relaxants / Xenopus oocytes / synthetic RNA / Two electrode voltage clamp / アフリカツメガエル |
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| Research Abstract |
The effects of agonists and competitive antagonists on bovine muscle adult- (junctional) and fetal-type (extrajunctional) bovine muscle nicotinic acetylcholine receptors (nAChR) have been compared by using Xenopus oocyte expression system, and the following results were obtained.
1. The Km values of the adult-type nAChR for acetylcholine (ACh) and succinyicholine (SCh) were not significantly different from those of the fetal-type The adult-type nAChR showed a faster time constant of current decay than the fetal-type did at 300 muM of ACh or SCh, when the currents were approximated by a single exponential function (p<0.05). At 1 mM, SCh exerted a potent blocking action of the open ion channel.
2. In double pulse experiments, the recovery from the desensitized state after application of ACh or SCh was faster in the case of the fetal-type nAChR than in the adult-type. tau_<rec> (the time constant of recovery from desensitization) of SCh was slower than that of ACh on both nAChRs. tau_<rec> at 10 muM of SCh was almost the same as that at 100 muM of ACh. These results suggest that the neuromuscular blockade caused by SCh is due to the slow rate of recovery from desensitization and that the difference between adult- and fetal-type nAChR is responsible for different desensitized states.
3. The Ki value of the adult-type nAChR for vecuronium, a competitive antagonist for nAChRs, was smaller than that of the fetal-type. When the sequence of addition and washout of ACh was repeated in the presence of vecuronium or beta-tubocurarine, both nAChRs showed remarkable difference in restoration of ACh- evoked currents and the adult-type showed the reduced response. These results suggest that a fraction of the channel blockade by vecuronium or beta-tubocurarine was borne in the non-competitive manner and the fraction appears to be large in the adult-type nAChR.
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