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Pacemaker mechanism of porcine sinoatrial node cells

Research Project

Project/Area Number 13670034
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionAkita University

Principal Investigator

ONO Kyoichi  Akita University School of Medicine, Associate Professor, 医学部, 助教授 (70185635)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordssinoatrial node / background K current / TASK / pacemaker current / sustained inward current / Delayed rectifier K current / T-type Ca current / L-type Ca current / 自動能 / イオンチャネル / シミュレーション / リスペリドン / 活動電位 / カリウムチャネル / ラット
Research Abstract

1) Background outward K^+ current in sinoatrial node cells: It is well known that in cardiac cells time-independent outward current extists positive potentials under the blockade of other voltage- and time-dependent current systems. We demonstrated that in rat atrial cells four transmembrane K^+ current, termed as TASK, acts as a background current whereas in rabbit sinoatrial node cells 4-aminopyridine-sensitive K^+ current plays this role. We consider that the background current plays an important role for repolarization of sinoatrial node cells.
2) Role of T-type Ca^<2+> channel in cardiac pacemaking: Effect of mibefradil on ionic currents of rabbit sinoatrial node cells were investigated in comparison to other dihyropiridines and Ni^<2+>. Mibefradil, efonidipine and nilvadipine, all of which blocked I_<CaL>, I_<CaT>, and I_<st3>, slowed the frequency of the spontaneous activity while maintaining the amplitude of the action potential. On the other hand, amlodipine, a selective I_<CaL … More > blocker, suppressed the action potential by reducing the amplitude. Ni^<2+> (50 μM), a I_<CaT> blocker, decreased the frequency only 20 %. We consider that the bradycardic action of efomidipine was derived, at least in part, from the suppression of I_<ca,T>. In addition, voltage- and frequency-dependent inhibition of I_<ca,L> and the block of Ist might contribute to the slowing of the pacemaker depolarization.
3) Drug-induced prolongation of action potential induced by drugs risperidone: Risperidone, a commonly used for terminating acute psychotic episodes and preventing recurrence of psychotic episodes in schizophrenics, inhibited IKr selectively in guinea-pig ventricular cells. On the other hand, inhalational anesthetics blocked IKs and produced a marked prolongation of the action potential.
4) On the basis of kinetics and density of ionic channels and ion transporters, we constructed a simulation model for sinoatrial node cells. The model includes 15 ionic channels and transporters known to be present in rabbit sinoatrial node cells, and reproduced the spontaneous action potential. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 尾野恭一: "T型カルシウムチャネルと心筋細胞ペースメーカー活性"CLIMCAL CALCIUM. 12. 797-803 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yazawa K, Ono K, Iijima T: "Modulation of mibefradil of the histamine-induced Ca^<2+> entry in human aortic endothelial cells"Japanese Journal of Pharmacology. 90. 125-130 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satoh E, Ono K, Xu F, Iijinm T: "Cloning and functional expression of a novel splice variant of rat TRPC4"Circulation Journal. 66. 954-958 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sarai N, Matsuoka S, Kuratomi S, Ono K, Noma A: "Role of individual ionic current systems in the SA node pacemaker activity hypothesized by a model study"Japanese Journal of Physiology. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono K: "T-type Ca^<2+> channels and cardiac pacemaker activity"Clinical Calcium. 12. 797-803 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yazawa K, Ono K, Iijima T: "Modulation of mibefradil of the histamine-induced Ca^<2+> entry in human aortic endothelial cells"Japanese Journal of Pharmacology. 90. 125-130 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saton E, Ono K, Xu F, Iijima T.: "Cloning and functional expression of a novel splice variant of rat TRPC4"Circulation Journal. 66. 954-958 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sarai N, Matsuoka S, Kuratomi S, Ono K, Noma A:: "Role of individual ionic current systems in the SA node pacemaker activity hypothesized by a model study"Japanese Journal of Physiology. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 尾野恭一: "T型カルシウムチャネルと心筋細胞ペースメーカー活性"CLINICAL CALCIUM. 12・6. 797-803 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yazawa K., Ono K., Iijima T.: "Modulation of mibefradil of the histamine-induced Ca^<2+> entry in human aortic endothelial cells"Japanese Journal of Pharmacology. 90・2. 125-130 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoh E., Ono K., Xu F., Iijima T.: "Cloning and functional expression of a novel splice variant of rat TRPC4"Circulation Journal. 66・10. 954-958 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sarai N., Matsuoka S., Kuratomi S., Ono K., Noma A.: "Role of individual ionic current systems in the SA node pacemaker activity hypothesized by a model study"Japanese Journal of Physiology. 2(印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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