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Molecular basis and electrophysiological properties of ion channels in rabbit sinoatrial node cells.

Research Project

Project/Area Number 12670697
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionTokyo Woman's Medical University

Principal Investigator

HAGIWARA Nobuhisa  Tokyo Women 's Medical University. Cardiology, Assistant Professor, 医学部, 助教授 (00180802)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsSinoatrial node / Transient outward current / Patch clamp method / Ito / Kv4.3 / 再分極相 / パッチクランプ法
Research Abstract

The electrophysiological properties of the transient outward current were investigated in voltageclamped single cells from the rabbit sino-atrial node. The current-voltage relationship exhibited a characteristic outward rectification with an activation threshold of -30 mV. External 4-aminopyridine inhibited this current in a dose-dependent manner (IC50 = 0.28 mM, Hill coefficient = 1.38). The steady-state inactivation exhibited a half-maximum voltage of -35 mV and a slope factor of -8.4 mV. The current density of the transient outward current was 6.3 ± 0.5 pA/pF in sino-atrial node cells and 12.3 ± 1.2 pA/pF in atrial cells. The inactivation time constant was faster in sino-atrial node cells (time constants, 4.2 ± 0.5 ms and 26.0 ± 0.6 ms, respectively, for the fast and slow components) than in atrial cells (9.7 ± 1.2 ms and 44.8 ± 3.2 ms, respectively). Recovery from inactivation was much faster in sino-atrial node cells (time constant, 44.7 ± 9.0 ms) than in atrial cells (time constants, 1.39 ± 0.32 s and 6.70 ± 0.1 s, respectively, for the fast and slow components). These results suggest that the kinetic properties, as well as the current density, of the transient outward current differs between sino-atrial node and atrial cells. Taking the current density of Ito at +10 mV as 2.5 ± 0.3 pA/pF gives a total Ito of approximately 100 pA at the. peak of the action potential in rabbit sino-atrial node cells. Thus, Ito may contribute significantly to the repolarization phase in mammalian sino-atrial node cells.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 関明子, 萩原誠久 他: "Effects of NIP-141 on K currents in human atrial myocytes"J. Cardiovasc. Pharmacol.. 39. 29-38 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 長崎陽子, 萩原誠久 他: "心房筋に特異性の高い新しい抗不整脈薬"内科. 89. 115-118 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 萩原誠久, 王軍 他: "洞結節細胞イオンチャネルの構造と機能"日本心臓血圧研究振興会(平成12年度業績集). 27-30 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 萩原誠久, 笠貫宏: "正常洞調律"不整脈, 笠貫 宏編集. 2-6 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 萩原誠久, 長崎陽子 他: "虚血心における不整脈の病態生理と治療"医学の歩み. 192. 96-101 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 萩原誠久: "伸展感受性Clチャネル"医学の歩み. 192. 1229-1230 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A, Seki., N, Hagiwara., H, Kasanuki.: "Effects of NIP-141 on K currents in human atrial myocytes."J. Cardiovasc. Pharmacol. 39. 29-38 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K, Kajimoto., T, Harada., K, Imamura., N, Matsuda., N, Hagiwara., H, Kasanuki.: "Efficacy of continuous intravenous drip infusion of disopyramide in hypertrophic obstructive cardiomyopathy during cardiogenic shock."J. Cardiol. 32. 197-203 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y, Nagasaki., N, Hagiwara., A, Seki., H, Kasanuki.: "Specific antiarrhythmic drugs for human atrium."Internal Medicine. 89. 115-118 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N, Hagiwara., Y, Nagasaki., A, Seki., H, Kasanuki.: "Mechanism of arrhythmia and its treatment associated with myocardial ischemia."Igakunoayumi. 192. 96-101 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A, Seki., N, Hagiwara., Y, Nagasaki., H, Kasanuki.: "Transient outward current in rabbit sinoatrial node cells."Jpn. Cric. J.. 64 Suppl. 496 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 関 明子, 萩原誠久 他: "Effects of NIP-141 on K currents in human atrial myocytes"Journal of Cardiovascular Pharmacology. 39. 29-38 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 萩原誠久: "アミオダロンの薬理作用 -ミステリアスドラッグの意味は-"Progress in Medicine. 21. 1688-1692 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 萩原誠久: "洞結節細胞イオンチャネルの構造と機能"日本心臓血圧研究振興会平成12年度研究業績集. 27-30 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 長崎陽子, 萩原誠久 他: "心房筋に特異性の高い新しい抗不整脈薬"内科. 89. 115-118 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 萩原誠久: "循環器疾患最新の治療:心臓ペースメーカーの選択と植え込み患者の管理"篠山重威, 矢崎義雄編集 南江堂. 552 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 関明子,萩原誠久 他: "Effects of NIP-141 on K currents in human atrial myocytes"Journal of Cardiovascular Pharmacology. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 萩原誠久,笠貫宏: "正常洞調律"不整脈笠貫宏稿集. 2-6 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 萩原誠久,長崎陽子 他: "虚血心における不整脈の病態生理と治療"医学の歩み. 192(1). 96-101 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 萩原誠久: "伸展感受性Clチャネル"医学の歩み. 192(13). 1229-1230 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 梶本克也,萩原誠久 他: "Efficacy of continuous intravenous drip infusion of disopyramide in hypertrophic obstructive cardiomyopathy during cardiogenic shock. "Journal of Cardiology. 35(3). 197-203 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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