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The grating mechanism of glycine receptor channels

Research Project

Project/Area Number 05454664
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurochemistry/Neuropharmacology
Research InstitutionGunma University School of Medicine

Principal Investigator

AKAGI Hiroyuki  Gunma Univ., Pharmacology Associate Prof., 医学部, 助教授 (30222508)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Ryoki  Gunma Univ., Pharmacology.Assistant.Prof., 医学部, 助手 (20212863)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1993: ¥4,900,000 (Direct Cost: ¥4,900,000)
KeywordsGlycine receptor / Xenopus oocytes / Molecular biology / Cl channel / グリシン受容体 / イオンチャネル / パッチクランプ / キメラ受容体
Research Abstract

The glycine receptor, is an integral anion-selective channel consisting of multiple subunit proteins. Using molecular cloning techniques, attempts were made to identify subunit proteins comprised in glycine receptor channels, and so far three kinds of alpha subunits (alpha1, alpha2, and alpha3) and one beta subunit have been clarified. Of these subunits the alpha proteins are of importance on the basis of receptor channel function. The alpha1 subunit consists of 449 amino acids and The alpha2 protein has 452 amino acids. The structural similarity between the two is 71% in amino acid sequence ; in particular, the amino-acid sequence of the putative transmembrane domains (TM1 to TM4) closely resembled each other. The structure of transmembrane domain in the alpha1 and alpha2 subunits is quite similar ; nevertheless a remarkable distinction was observed for the kinetics between the two channels. The mean open time of the alpha1 channel expressed in Xenopus oocytes was very short (-4 msec) while that of the alpha2 was relatively longer (-280 msec). A few acids in the channel domain are responsible for the gating mechanism of the glycine receptor channels. The difference in the kinetics may also be relevant to plasticity of the glycinergic transmission. In order to disclose the difference of kinetic mechanisms in these two channels, I constructed several numbers of cDNAs encoding the mutated alpha1/alpha2 channels. Although these mutant receptors expressed in oocytes have the ability to generate glycine-induced membrance currents, their relative amplitudes were 10-30 times as low as those of wild-type channels when the whole-cell currents were measured ; therefore it was very difficult to analyze the single-channel properties with the excised out side-out patches. Attempts to improve the efficiency of translation in oocytes are still undergoing.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Uchiyama M.et al.: "Down-regulation of glyciore receptor channels by protein kinasec expressed in Xemopus oogtes" Mol.Brain Res.24. 295-300 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] AKAGI,H.et al.: "Function and madulation of the cloned glycine receptor channels expressed in Xemopus oogutes" Jap.J.Physiol.44. 91-96 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 赤木宏行(分担): "能機能の解明" 創風社, 286 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 赤木宏行(分担): "ブレインサイエンス最前線'95" 講談社サイエンティフィック, 131 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Uchiyama, M.et al.: "Down-regulation of glycine receptor channels by protein kinases C expressed in Xenopus oocytes." Mol.Brain Res.24. 295-300 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akagi, H., et al.: "Function and modulation of the cloned glycine receptor channels expressed in Xenopus oocytes" Jap.J.Physiol.44. 91-96 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Uchiyama M.,et al: "Down-regulation of glycine receptor channels by protein kinase" Molecular Brain Res.24. 295-300 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] AKAGI H., et al: "Function and modulation of the Cloned glycine receptr channels expressed in Xenopus oocytes" Jap.J.Physiol. 44. 91-96 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 赤木宏行(分担): "脳機能の解明" 創風社, 286 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 赤木宏行(分担): "ブレインサイエンス最前線 '95" 講談社 サイエンティフィク, 131 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Uchiyama,M.: "Down-regulation of glycine receptor channels by protein Kinase C in Xenopus oocytes injected with synthetic DNA." Molecular Brain Research. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Akagi,H.: "Function and modulation of cloned glycine receptor channels expressed in Xenopus oocytes" Japanese Journal of Physiology. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] 赤木宏行: "レセプター、基礎と臨床" 朝倉書店, 944 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 赤木宏行: "イオンチャネル・1" メジカルビコー社, 226 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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