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Studies on the developmental changes and species difference of cardiac function : analysis of the electrophysiological characteristics and specific responses to alpha-adrenergic stimulation in mice

Research Project

Project/Area Number 09670107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionToho University

Principal Investigator

KOKI Shigenobu  Toho University Pharmacology Professor, 薬学部, 教授 (50012654)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsMyocardium / Mouse / Action potential / Sarcoplasmic reticulum / Postnatal development / Endothelial cells / Angiotensin / Endothelin / エンドセリンI, / アンジオテンシンII / 変力作用 / プロスタグランジン / アセチルコリン / 収縮機構 / 発達変化 / 交感神経α作用 / カルシウムチャネル
Research Abstract

Specificity of mice myocardium and its functional changes during development were examined from various points of veiw (electrophysiology, contractile mechanisms, drug sensitivity, etc.). Main results obtained are as follows.
1)Action potentials with relatively long duration at neonatal stages were changed into those with extremetly short duration without plateau phase in the adult. This characteristic action potential configuration was considered to be due to small calcium current and large transient outward current, which was essentially the same as that observed in rat myocardium. During development, calcium current seemed to decrease with age.
2)Contraction of adult myocardium was suggested to be highly dependent on SR function whereas the dependency was low in neonatal myocardium. This change was qualitatively similar to that observed in rat myocardium, but the degree of developmental change was small compared to rat.
3)Developmental conversion of inotropism from positive to negative was observed in the responses to endothelin I and angiotensin II, which was similar to that observed with alpha-adrenergic stimulation. Receptor subtypes did not change during development (ETA and AT1, respectively)
4)Acetylcholine produced positive inotropic response in mouse atria, which was totally different from other animal species. On the basis of various experimental results, it was suggested that acetylcholine may release prostaglandin(s) from endocardial endothelial cells, which in turn producced positive inotropism.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] H.Tanaka, ---, and K.Shigenobu: "Role of sarcoplasmic reticulum in myocardial contraction of neonatal and adult mice" Comparative Biochem.Physiol.PartA. 120. 431-438 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Sekine, --- and K.Shigenobu: "Developmental conversion of inotropism by endothelin I and angiotensin II from positive to negative in mice" European J.Pharmacology. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka H., Sekine T., Shigenobu K.: "Role of sarcoplasmic reticulum in myocardial contraction of neonatal and adult mice." Comp.Biochem.Physiol.120. 431-438 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sekine T., Kusano H., Nishimaru K.Tanaka Y., Tanaka H., and Shigenobu K.: "Developmental conversion of inotropism by endothelin and angiotensin II from positive to negative in mice" European J.of Pharmacology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Sekine,and K.Shigenobu: "Developmental conversion of inotropism by endothelin I and angiotensin II from positive to negative in mice" Europ.J.Pharmacology. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Tanaka, T.Sekine, K.Nishimaru, K.Shigenobu: "Role of sarcoplasmic reticulum in myocardial contraction of neonatal and adult mice" Comparative Biochemistry and Physiology. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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