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1998 Fiscal Year Final Research Report Summary

The effects of muscle relaxants on adult-type and fetal-type nictinic acetylcholine receptors

Research Project

Project/Area Number 09671566
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionYamaguchi University

Principal Investigator

YAMADA Yasue  Yamaguchi : University School of Medicine, Assistant, 医学部, 助手 (00166737)

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)
Project Period (FY) 1997 – 1998
KeywordsNicotinic acetylcholine receptor / Neuromuscular junction / Acetylcholine / Succinylcholine / Muscle relaxants / Xenopus oocytes / synthetic RNA / Two electrode voltage clamp
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.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Yasue Yamada: "Modulation of the channel activity of ε2/ζ1-subtypeN-metyl-D-aspartate receptor by PSD-95." J.Biol.Chem.274(10). 6647-6652 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sachie Inouye: "Distribution and development changes of adenylate kinase isozyme in the rat brain : Localization of adenylate kinase 1 in the olfactory bulb." Biochem.Biophys.Res.Commun.254. 618-622 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sachie Inouye: "Increase of adenylate kinase isozyme 1 protein during neuronal differentiation in mouse embryonal carcinoma P19 cells and in rat brain primary cultured cells." J.Neurochem.71(1). 125-133 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masahide Iga: "Characterization of the Interaction between synspsin 1 and Calspectin." Biochem.Biophys.Res.Commun.231. 852-855 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshihiro Kimura: "Phopholamban domain Ib mutations influence functional interactions with the Ca2+-ATPase isoform of cardiac sarcoplasmic reticulum." J.Biol.Chem.273(23). 14238-14241 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshihiro Kimura: "Phospholamban domain I/cytochrome b5 transmembrane sequence chimera do not inhibit SERCA2a." FEBS Lett.425. 509-512 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Inui: "Biomembranes" Academic Press, 21 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasue Yamada: "Modulation of the channel activity of epsilon2/zeta1-subtype N-metyl-D-aspartate receptor by PSD-95." J.Biol.Chem.274 (10). 6647-6652 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sachie Inouye: "Disstibution and development changes of adenylate kinase Localization of adenylate kinase 1 in the olfactory bulb." Biochem.Biophys.Res.Commun.254. 618-622 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sachie Inouye: "Increase of adenylate kinase isozyme 1 protein during neuronal differentiation in mouse embryonal carcinoma P19 cells and in rat brain primary cultured cells." J.Neurochem.71 (1). 125-133 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahide Iga: "Characterization of the Interaction between synspsin 1 and Calspectin." Biochem.Biophys.Res.Commun.231. 852-855 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makoto Inui: "Reconstitution of calcium pumping of cardiac sarcoplasmic reticulum." In Biomembranes Academic Press. 825-831 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makoto Inui: "Purification of Ca^<2+> release channel (ryanodine receptor) from heart and skeletal muscle sarcoplasmic reticulum." In Biomembranes Academic Press. 854-860 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshihiro Kumura: "Phospholamban domain I/cytochrome b5 transmembrane sequence chimera do not inhibit SERCA2a." FEBS Lett.425. 509-512 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshihiro Kumura: "Phospholamban domain Ib mutations influence functional interactions with the Ca^<2+>-ATPase isoform of cardiac sarcoplasmic reticulum." J.Biol.Chem.273 (23). 14238-14241 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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