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Pharmacological approach toward the pacemaker mechanism of porcine sinoatrial node cells

Research Project

Project/Area Number 10670080
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionAKITA UNIVERSITY

Principal Investigator

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

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordssinoatrial node / automaticity / pacemaker current / delayed rectifier potassium current / hyperpolarization-activated cation current / chromanol 293B / pig / ion channels / ペースメーカー電流 / イオンチャンネル / 心臓自動能 / 遅延整流Kチャネル / 持続性内向き電流
Research Abstract

This project was carried out to investigate the mechanisms underlying the automaticity of porcine sinoatrial node cells, and the following results were obtained.
1. The isolated cells exhibited spontaneous action potentials at a rate of approximately 80 minィイD1-1ィエD1. This value is similar to the heart rate of pigs and slower than that of rabbit sinoatrial node cell (approximately 200 minィイD1-1ィエD1), indicating that the heart rate is determined by intrinsic properties of sinoatrial node cells of various mammalian species.
2. In porcine sinoatrial node cells the delayed rectifier KィイD1+ィエD1 current (IィイD2KィエD2) is largely derived from the slowly activating IィイD2KィエD2 (IィイD2KsィエD2). The result suggest that IィイD2KsィエD2 may, in part, account for the relatively slower heart rate of pigs than rabbit in which the rapidly activating IィイD2KィエD2 (IィイD2KrィエD2) is predominant component of IK.
3. The hyperpolarization-activated cation current (IィイD2hィエD2) activates at membrane potentials more negative … More than -70 mV. The kinetics and ionic selectivity were essentially similar to IィイD2hィエD2 of rabbit sinoatrial node cells.
4. Chromanol derivative 293B blocks IィイD2KsィエD2 selectively. In guinea-pig ventricular cells, block by chromanol 293B of IィイD2KsィエD2 occurred in a time-dependent manner. We conclude that chromanol 293B is an open channel blocker for IィイD2KsィエD2 with a relatively slower blocking rate constant than those reported so far for time- and voltage-dependent blockade of ionic channels.
It has been reported that various ionic currents such as IィイD2KィエD2, IィイD2hィエD2, L- and T-type CaィイD12+ィエD1 currents, NaィイD1+ィエD1/KィイD1+ィエD1 pump current, background cation current, muscarinic KィイD1+ィエD1 current and dyhydropyridine-sensitive NaィイD1+ィエD1 current, contribute to the automaticity of sinoatrial node cells. Although we could successfully quantify the properties of IK and Ih in porcine sinoatirial node cells in this project, the characteristics of other ionic currents still remain to be evaluated. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] K.Ono: "Chloride-sensitive nature of the histamine-induced Ca^<2+> entry in cultured human aortic endothelial cells"Journal of Physiology. 511. 837-849 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Nakao: "Mechanical stress-induced Ca^<2+> entry and Cl^- current in cultured human aortic endothelial cells"American Journal of Physiology. 276. C238-C249 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Shibata: "Inhibition by genistein of the hyperpolarization-activated cation current in porcine sino-atrial node cells"British Journal of Pharmacology. 128. 1284-1290 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Ono: "Properties of the delayed rectifier potassium current in porcine sino-atrial node cells"Journal of Physiology. 524. 51-62 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Nakao: "Inhibition by antisense oligonucleotides of plasma membrane ATPase in vascular endothelial cells"European Journal of Pharmacology. 387. 273-277 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Fujisawa: "Time-dependent block of the slowly activating delayed rectifier K^+ current by chro-manol 293B in guinea-pig ventricular cells"British Journal of Pharmacology. 129. 1007-1013 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. ONO: "Chloride-sensitive nature of the histamine-induced CaィイD12+ィエD1 entry in cultured human aortic endothelial cells."Journal of Physiology. 511. 837-849 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. NAKAO: "Mechanical stress-induced CaィイD12+ィエD1 entry and ClィイD1-ィエD1current in cultured human aortic endothelial cells."American Journal of Physiology. 276. C238-C249 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. SHIBATA: "Inhibition by genistein of the hyperpolarization-activated cation current in porcine sino-atrial node cells."British Journal of Pharmacology. 128. 1284-1290 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. ONO: "properties of the delayed rectified potassium current in porcine sino-atrial node cells."Journal of Physiology. 524. 51-62 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. NAKAO: "Inhibition by antisense oligonucleotides of plasma membrane ATPase in vascular endothelial cells."European Journal of Pharmacology. 387. 273-277 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. FUJISAWA: "Time-dependent block of the slowly activating delayed rectifier KィイD1+ィエD1 current by chromanol 293B in guinea-pig ventricular cells."British Journal of Pharmacology. 129. 1007-1013 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Nakao: "Mechanical stress-induced Ca^<2+> entry and Cl^- current in cultured human aortic endothelial cells"American Journal of Physiology. 276. C238-C249 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S. Shibata: "Inhibition by genistein of the hyperpolarization-activated cation current in porcine sino-atrial node cells"British Journal of Pharmacology. 128. 1284-1290 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Ono: "Properties of the delayed rectifier potassium current in porcine sino-atrial node cells"Journal of Physiology. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] M. Nakao: "Inhibition by antisense oligonucleotides of plasma membrane ATPase in vascular endothelial cells"European Journal of Pharmacology. 387. 273-277 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] S. Fujisawa: "Time-dependent block of the slowly activating delayed rectifier K^+ current by chromanol 293B in guinea-pig ventricular cells"British Journal of Pharmacology. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Ono,M.Nakao and T.Iiji-maw: "Chlorode-sensitive nature of the histamine-induced Ca^<2+> entry in cultured human aortic endothelial cells." Journal of Physiology. 511. 837-849 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Nakao,K.Ono and T.Iijima: "Mechanical stress-induced Ca^<2+> entry and Cl^- current in cultured human aortic en-dothelial cells." Journal of America Journal of Physiology. H276. C238-C249 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Ono,S.Shibata and T.Iijima: "Action potential and membrane currents in porcine sino-atrial node cells." Japamese Journal of Physiology. Suppl 48. S73-S73 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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