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2002 Fiscal Year Final Research Report Summary

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
Keywordssinoatrial node / background K current / TASK / pacemaker current / sustained inward current / Delayed rectifier K current / T-type Ca current / L-type Ca current
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

  • Research Products

    (8 results)

All Other

All Publications (8 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2004-04-14  

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