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Regulation of the cardiac delayed rectifier K^+ channel by membrane phosphoinositides

Research Project

Project/Area Number 13670042
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionShiga University of Medical Science

Principal Investigator

MATSUURA Hiroshi  Shiga University of Medical Science, Physiology, Professor, 医学部, 教授 (60238962)

Co-Investigator(Kenkyū-buntansha) TOYODA Futoshi  Shiga University of Medical Science, Physiology, Assistant Professor, 医学部, 助手 (90324574)
DING Wei-Guang  Shiga University of Medical Science, Physiology, Assistant Professor, 医学部, 助手 (80242973)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsdelayed rectifier K^+ current / I_<ks> / phosphatidylinositol 4, 5-bisphosphate / PtdIns(4, 5)P_2 / wortmannin / anti-PtdIns(4, 5)P_2, monoclonal antibodies / neomycin / electrostatic interactions / パッチクランプ法 / イノシトールリン脂質 / ホスファチジルイノシトール4.5二リン酸 / 抗体 / 遅延整流性K^+チャンネル / 緩徐活性型遅延整流性K^+チャンネル / ポリアミン / スペルミジン / ホスファチジルイノシトール4,5二リン酸 / 緩徐活性型遅延整流性K^+チャネル
Research Abstract

Regulation of the slowly activating component of delayed rectifier K^+ current (I_<ks>) by the membrane phospholipid phosphatidylinositol 4, 5-bisphosphate (PtdIns(4, 5)P_2) was examined in guinea-pig atrial cells using whole-cell patch-clamp method. Intracellular application of 50 μM wortmannin through a recording pipette evoked progressive increase in I_<ks> over a 10-15 min to 208.5±14.6% (n = 9) of initial magnitude obtained shortly after rupture of the patch membrane, when assessed by measuring the amplitude of tail current elicited upon return to a holding potential of -50 mV following a 2-s depolarization to +30 mV. Intracellular application of anti-PtdIns(4, 5)P_2 monoclonal antibodies also increased the amplitude of I_<ks> tail current to 198.4±19.9% (n = 5). In contrast, intracellular loading of atrial cells with exogenous PtdIns(4, 5)P_2 (100μM) produced a marked decrease in the amplitude of I_<ks> tail current to 44.8±8.2% (n = 5). These results strongly suggest that endogenous membrane PtdIns(4, 5)P_2 produces a potent inhibitory action on I_<ks> channels. Intracellular application of neomycin (50 μM) or aluminum (50 μM) evoked an increase in the amplitude of I_<ks> tail current to 161.0±13.5% (n = 4) and 150.0±8.2% (n = 4), respectively, which suggests that I_<ks> channel is inhibited by membrane PtdIns(4, 5)P_2 through electrostatic interactions with negatively charged head group on PtdIns(4, 5)P_2. Enhancement of I_<ks> by P2Y receptor stimulation with 50 μM ATP was almost totally abolished by exogenously applied PtdIns(4, 5)P_2. This result suggests that depletion of membrane PtdIns(4, 5)P_2 is primarily involved in an enhancement of I_<ks> evoked by stimulation of P2Y receptor in guinea-pig atrial cells.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Matsuura, H.: "Rapidly and slowly activating components of delayed rectifier K^+ current in guinea-pig sino-atrial node pacemaker cells"J Physiol. 540. 815-830 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sanada, M.: "Increase in intracellular Ca^<2+> and calcitonine gene-related peptide release through metabotropic P2Y receptors in rat dorsal root ganglion neurons"Neuroscience. 111. 413-422 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu, K.: "Potentiation of slow component of delayed rectifier K^+ current by cyclic GMP via two distinct mechanisms : inhibition of phosphodiesterase 3 and activation of protein kinase G"Br J Pharmacol. 137. 127-137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ding, W.G.: "Blocking action of chromanol 293B on the slow component of delayed rectifier K^+ current in guinea-pig sino-atrial node cells"Br J Pharmacol. 137. 253-262 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Omatsu-Kanbe, M.: "Multiple P2 receptors contribute to a transient increase in intracellular Ca^<2+> concentration in ATP-stimulated rat brown adipocytes"Exp Physiol. 87. 643-652 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamada, K.: "Properties of the Na^+/K^+ pump current in small neurons from adult rat dorsal root ganglia"Br J Pharmacol. 138. 1517-1527 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuura,H., Ehara,T., Ding,W.G., Omatsu-Kanbe,M., Isono,T.: "Rapidly and slowly activating components of delayed rectifier K^+ current in guinea-pig sino-atrial node pacemaker cells"J Physiol. 540. 815-830 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sanada,M., Yasuda,H., Omatsu-Kanbe,M., Sango,K., Isono,T., Matsuuta,R., Kikkawa,R.: "Increase in intracellular Ca^<2+> and calcitonine gene-related peptide release through metabotropic F2Y receptors in rat dorsal root ganglion neurons"111. 413-422 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu,K., Shintani,Y., Ding,W.-G., Matsuura,H., Bamba,T.: "Potentiation of slow component of delayed rectifier K^+ current by cyclic GMP via two distinct mechanisms : inhibition of phosphodiesterase 3 and activation of protein kinase G"Br J Pharmacol. 137. 127-137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ding,W.-G., Toyoda,F., Matsuura,H.: "Blocking action of chromanol 293B on the slow component of delayed rectifier K^+ current in guinea-pig sino-atrial node cells"Br J Pharmacol. 137. 253-262 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Omatsu-Kanbe,M., Isono,T., Matsuura,H.: "Multiple P2 receptors contribute to a transient increase in intracellular Ca^<2+> concentration in ATP-stimulated rat brown adipocytes"Exp Physiol. 87. 643-652 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamada,K., Matsuura,H., Sanada,M., Toyoda,F., Omatsu-Kanbe,M., Kashiwagi,A., Yasuda,H.: "Properties of the Na^+/K^+ pump current in small neurons from adult rat dorsal root ganglia"Br J Pharmacol. 138. 1517-15217 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu, K.: "Potentiation of slow component of delayed rectifier K^+ current by cyclic GMP via two distinct mechanisms: inhibition of phoshodiesterase 3 and activation of protein kinase G."Br. J. Pharmacol.. 137. 127-137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ding, W.-G.: "Blocking action of chromanol 293B on the slow component of delayed rectifier K^+ current in guinea-pig sino-atrial node cells."Br. J. Pharmacol.. 137. 253-262 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Omatsu-Kanbe, M.: "Multiple P2 receptors contribute to a transient increase in intracellular Ca^<2+> concentration in ATP-stimulated rat brown adipocytes."Exp. Physiol.. 87. 643-652 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hamada, K.: "Properties of the Na^+/K^+ pump current in small neurons from adult rat dorsal root ganglia."Br. J. Pharmacol.. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuura, H.: "Rapidly and slowly activating components of delayed rectifier K^+ current in guinea-pig sino-atrial node pacemaker cells"J Physiol. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sanada, M.: "Increase in intracellular Ca^<2+> and calcitonin generelated peptide release through metabotropic P2Y receptors in rat dorsal root ganglion neurons"Neuroscience. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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