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Inward rectification and voltage-dependent activation of HERG K channels

Research Project

Project/Area Number 08670055
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) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsHERG / sinoatrial node / delayd rectifier K current / pacemaker activity / IKr / IKs / 洞房結節 / Caイオン
Research Abstract

We have demonstrated that the conductance and kinetics of I_K in SA node cells closely resembled those of the rapidly activating component of I_K (I_<Kr>) which is coded by human eag-related gene (HERG), in terms of ion selectivity, gating parameters of activation, inward rectification of the steady-state IV relation, the single channel conductance, and selective blockage by class III antiarrythmic agents. The inward rectifying property was characterized by decrease of open probablity at positive potentials. Under the inside-out mode, the open probabilty did not increase even if the patch membrane was exposed to the solution containing on Mg^<2+> or Ca^<2+>, indicating that the inward rectification is not due to block by these cations but derived from the intirinsic gating of the I_<Kr> channels.
When the external Ca^<2+> was removed, the decay of the tail current was markedly prolonged. The effect of external Ca^<2+> was voltage-and concentration-dependent. The results indicate that the gating of I_<Kr>, which has been believed to be an intrinsic voltage-dependent mechanism, might be caused by a time-and voltage-dependent block and unblock of the I_<Kr> channels by external Ca^<2+>.
I_<Kr> is essential in maintaining the automaticity of rabbit SAN cells. To extend this hypothesis to other species, we made an attempt to isolate pacemaker cells from porcine hearts. The isolated cells exhibited spontaneous activity with beating rate of approximately 80 min-1 in normal Tyrode solution. It was found that the delayd rectifier K^+ current of porcine SAN cells consisted of the slowly activating delayd rectifier K + current, in contrast to I_<Kr> of rabbit. The different I_K might contribute to different heart rate among various species.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Y.Tajima, K. Ono and N.Akaike: "Perforate Patch-clamp recording in cardiac myocytes using cation-selective ionophre gramicidin" American Jounal of Physiology. 271. C524-C532 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] J.Guo, K.Ono and A.Noma: "Monovalent cation conductance of the sustained current in rabbit sinoatrial node cells" Pflugers Archiv. 433. 209-211 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Harata., J.Wn., H.Ishibashi., K.Ono and N.Akaike: "Run-down of the GABA_A responese under experimental ischemia in acutely dissociated CAl pyramidal neurones" Jouranl Physiology. 500. 673-688 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] A.Shinbo., K.Ono and T.Iijima: "Activation of cardiac ATP-sensitive K^+ channels by KRN4884,a novel K^+ channels opener" Jouranl Physiology and Experimental Therapeutics. 283. 770-777 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ono, M.Akao and T.Iijima: "Chloride-and voltage-dependent Ca^<2+> transient in cultured human aortic endothelial cells" Heart and Vessels. Suppl 12. 50-52 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 尾野 恭一: "同房結節遅延整流K電流の解析" Therapautic Research. 18. 3537-3542 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Tajima, K.Ono and N.Akaike: "Perforate patch-clamp recording in cardiac selective ionophore gramicidin." American Journal of Physiology. 271. C524-C532 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] J.Guo, K.Ono and A.Noma: "Monovalent cation conductance of the sustained inward current in rabbit sinoatrial node cells." Pflugers Archiv. 433. 209-211 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Harata., J.Wu., H.Ishibashi., K.Ono and N.Akaike: "Rundown of the GABA_A response under experimental ischemia in acutely dissociated CA1 pyramidal neurones." Jouranl of Physiology. 500. 673-688 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] A.Shinbo., K.Ono and T.Iijima: "Activation of cardiac ATP-sensitive K^+ channels by KRN4884, a novel K^+ channel opener." Journal of Pharmacology and Experimental Therapeutics. 283. 770-777 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ono, M.Nakao and T.Iijima: "Chloride-and voltage-dependent Ca^<2+> transient in cultured human aortic endothelial cells." Heart and Vessels.Suppl. 12. 50-52 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ono: "Analysis of the delayd rectifier K^+ current in cardiac pacemaker cells." Therapeutic Research. 18. 3537-3542 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Harata., J.Wu., H.Ishibashi., K.Ono and N.Akaike: "Run-down of the GABA_A response under experimental ischemia in acutely dissociated CA1 pyramidal neurones" Jouranl of Physiology. 500. 673-688 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Shinbo., K.Ono and T.Iijima: "Activation of cardiac ATP-sensitive K^+ channels by KRN4884,a novel K^+ channel opener" Journal of Pharmacology and Experimental Therapeutics. 283. 770-777 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Ono, M.Nakao and T.Iijima: "Chloride-and voltage-dependent Ca^<2+> transient in cultured human aortic endothelial cells" Heart and Vessels. Suppl 12. 50-52 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 尾野恭一: "洞房結節遅延整流K電流の解析" Therapeutic Research. 18. 3537-3542 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tajima Y.,Ono K.& Akaike N.: "Perforated patch-clamp recording in cardiac myocytes using cation-selective ionophore gramicidin" American Journal of Physiology.271. C524-C532 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.Guo.,Ono K.& Noma A.: "Monovalent cation conductance of the sustained inward current in rabbit sinoatrial node cells" Pflugers Arch.433. 209-211 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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