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A Research for L-type Calcium Channel Modulation by b2-adrenergic Stimulation

Research Project

Project/Area Number14570698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionTeikyo University School of Medicine

Principal Investigator

FURUKAWA Taiji  Teikyo University, School of Medicine, Lecturer, 医学部, 講師 (70276731)

Project Period (FY) 2002 – 2003
Project Status Completed(Fiscal Year 2003)
Budget Amount *help
¥2,500,000 (Direct Cost : ¥2,500,000)
Fiscal Year 2003 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 2002 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Keywordscalcium channel / beta receptor / GPT binding protein
Research Abstract

We measured the effects of beta-adrenergic stimulations on L-type calcium channel in Xenopus oocyte expression system. L-type calcium channel (alpha 1 C) was co-expressed with calcium channel alpha2, beta2a subunits and stimulatory GPT binding protein (Gs). Adenylate cyclase, beta2-adrenergic receptor and PKA binding protein (AKAP79) were also co-expressed in various combinations of these proteins. Membrane current through expressed calcium channel was measured by conventional two-microelectrodes voltage clamp methods. cDNA for these proteins were already cloned and we produced cRNA for each proteins using in-vitro-transcription method. Microinjections of the combination of various cRNA were performed, and measured the effect of beta-stimulation by isoproterenol on the modulation of membrane current amplitude. However, no combination of the protein re-constructs the beta-adrenergic stimulation of L-type calcium channel, which is common in both skeletal muscles and myocytes.
We changed the expressing alphal subunit of calcium channel from alphalC to alphalA (P/Q-type). We observed PKA stimulation of the channel, and Rp-cAMPS and H89, PKA inhibitory agents, decreased the membrane current. We are planning to investigate the structure-function relationships of the two alphal subunits.
During the investigation we measured the effect of numerous calcium channel antagonists using the same expression system. The results were published as the supported research.

Report

(3results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report

Research Products

(5results)

All 2005 2004 Other

All Journal Article

  • [Journal Article] Differential blocking action of dihydropyridine Ca^<2+> antagonists on a T-type Ca^<2+> channel (α_<1G>) expressed in Xenopus oocytes.2005

    • Author(s)
      T.Furukawa et al.
    • Journal Title

      Journal of Cardiovascular Pharmacology In press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca^<2+> channels2004

    • Author(s)
      T.Furukawa et al.
    • Journal Title

      British Journal of Pharmacology 143

      Pages : 1050-1057

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Negative regulation of opioid receptor-g protein-Ca2+ channel pathway by the nootropic nefiracetam2004

    • Author(s)
      M.Yoshii et al.
    • Journal Title

      Annals of the New York Academy of Sciences 1025

      Pages : 389-397

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Negative regulation of opioid receptor-G protein-Ca^<2+> channel pathway by the nootropic nefiracetam2004

    • Author(s)
      M.Yoshii et al.
    • Journal Title

      Annals of the New York Academy of Sciences 1025

      Pages : 389-397

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Differential blocking action of dihydropyridine Ca^<2+> antagonists on a T-type Ca^<2+> channel (α_<1G>) expressed in Xenopus oocytes.

    • Author(s)
      T.Furukawa et al.
    • Journal Title

      Journal of Cardiovascular Pharmacology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary

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Published : 2002-04-01   Modified : 2016-04-21  

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