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1990 Fiscal Year Final Research Report Summary

Physiological Modulations of Cardiac K^+ Currents by Ca^<2+> and their Roles for Arrhythmogenesis

Research Project

Project/Area Number 01480245
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionMedical Research Institution, Tokyo Medical and Dental University

Principal Investigator

HIRAOKA Masayasu  Tokyo Medical and Dental University, Medical Research Institution Professor, 難治疾患研究所, 教授 (80014281)

Co-Investigator(Kenkyū-buntansha) HIRANO Yuji  Tokyo Medical and Dental University, Medical Research Institution Instructor, 難治疾患研究所, 助手 (00181181)
SAWANOBORI Tohru  Tokyo Medical and Dental University, Medical Research Institution Associate Prof, 難治疾患研究所, 助教授 (00014217)
Project Period (FY) 1989 – 1990
KeywordsSingle heart cells / Patch-clamp technique / Whole-cell current recordings / Transient outward current / Delayed outward K^+ current / Ca^<2+>-influx / Increased internal Ca^<2+>
Research Abstract

In this research project, we studied two types of K+ currents in isolated vetricular myocytes from guinea-pig and rabbit hearts using the patch-clamp technique of the whole-cell configurations. The one type was the transient outward current (I_<to>) recorded from rabbit myocytes and the other was the delayed outward K^+ current (I_k) from guinea-pig myocytes. I_<to> was activated by step depolarizations positive to -20 mV I_<to> was found to be composed of two components, the Ca^<2+>-insensitive and Ca^<2+>-sensitive components. The Ca^<2+>-insensitive I_<to> was easily blocked by 4-aminopyridine and the Ca^<2+>-sensitive one was inhibited by caffeine. The latter component was also abolished by removing extracellular Ca^<2+> or application of Ca^<2+> blocking agents. It was inhibited by application of ryanidine. All of these results suggest that the Ca^<2+>-sensitive I_<to> was activated by Ca^<2+>-influx via the Ca^<2+> channel and/or increased internal Ca^<2+> through the Ca^<2+> rel … More ease from SR. The Ca^<2+>-sensitive I_<to> was increased during rapid stimulation and, therefore, it contributed the formation of the notch on action potential repolarization and its shortening during tachycardia.
I_K was activated by depolarization positive to -50 mV and it contributed to the final repolarization phase. From the kinetic analysis of the tail current, I_k was separated by two components with a rapid and slow activation. The fast activating I_k was sensitive to Ca^<2+>-influx. Therefore, the inhibition of the Ca^<2+>-influx either by Ca^<2+> free solution or application of the Ca^<2+> antagonists produced a paradoxical prolongation of action potential duration, which was attributed to suppression of the fast activating I_k. The behaviors of I_k and action potential repolarizations were well simulated by the modulation of I_k by changes in internal Ca^<2+>. Co^<2+> was often used as a blocker of the Ca^<2+> channel but it also inhibited I_k at comparable concentrations. The mechanisms of the I_k block by Co^<2+> were shown to be screening the negative surface charges, decreasing the functional channel and additional voltage-dependent process. Therefore, Co^<2+> blocked I_k by multiple mechanisms. Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 沢登 徹, 平岡 昌和: "単一心筋における異常自動能." 薬理と治療. 18(Suppl). 275-283 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平岡 昌和: "心筋膜発電現象ー心電現象の源" BME. 4. 48-57 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平岡 昌和: "カリウムチャネルー研究の現状と臨床応用への展望" Therap.Res.11. 3497-3510 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawano,S.and M.Hiraoka: "Transient outward currents and action potential alterations in rabbit ventricular myocytes." J.Mol.Cell.Cardiol.(1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平岡 昌和: "心筋のカリウムチャネル" 心臓. (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fan,Z.and M.Hiraoka: "Depression of the delayed outward K^+ current by Co^<2+> in guineaーpig ventricular myocytes." Am.J.Physiol.(Cell Physiol.). (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fan,Z.and M.Hiraoka: "Ca^<2+>ーdependent activation of delayed outward K^+ current determining action potential duration in guineaーpig ventricular myocytes." (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirano,Y.,S.Abe,T.Sawanobori & M.Hiraoka: "Extracellular ATPーinduced Ca^<2+> transients in mammalian atrial myocytes." Jpn.J.Physiol.40(Suppl). 268 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平野 裕司 ・ 范 錚 ・ 沢登 徹 ・平岡 昌和: "心室筋活動電位のシミュレ-ション,頻度依存性と細胞内Ca^<2+>濃度変動の寄与." 心電図. 10. 671 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawano, S. & M. Hiraoka :"Transient outward currents and action potential alterations in rabbit ventricular myocytes." J. Mol. Cell. Cardiol.(1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fan, Z. and M. Hiraoka :"Depression of the delayed outward K^+ current by Co^<2+> in guineaーpig ventricular myocytes." Am. J. Physiol.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fan, Z. & M. Hiraoka :"Ca^<2+>ーdependent activation of delayed outward K^+ current determining action potential duration in guineaーpig ventricular myocytes."

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirano, Y., S. Abe, T. Sawanobori & M. Hiraoka :"Extracellular ATP-induced Ca^<2+> transients in mammalian atrial myocytes." Jpn. J. Pharmacol.,. 52 (Suppl. 2). 111 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirano, Y., T. Sawanobori, M. Hiraoka and S. Abe :"Extracellular ATP-induced Ca^<2+> transients in mammalian atrial myocytes." Jpn. J. Physiol.40 (Suppl.). S268 (1990)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-08-12  

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