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Cell biological analysis of KATP channel in ischemic myocardium

Research Project

Project/Area Number 13670707
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

OTANI Hideo  KYOTO UNIVERSITY, DEPT.MEDICINE, ASSISTANT PROF., 医学研究科, 助手 (60293867)

Co-Investigator(Kenkyū-buntansha) HORIE Minoru  KYOTO UNIVERSITY, DEPT.MEDICINE, ASSOCIATE PROF., 医学研究科, 講師 (90183938)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsKATP channel / KCNQ1 / cell swelling / QT prolongation / myocardial ischemia / LQTs / SCN5A / KCNJ2 / QT延長症候群 / Andersen症候群 / 不整脈 / 虚血心筋保護 / Kir6.1 / SUR / CFTR / アンギオテンシンII
Research Abstract

intracellular ATP level. Especially, in ischemic myocardium, K ATP channel is known to be one of the most important component, and several other channels which are modulated by intracellular ATP level. are also contributing by determining. action potential duration. We analyzed the function of these channel... by patch-clump method in cultured cells which overexpressing KCNQ1, the subunit of delayed rectifier K channel. Analyses using tyrosin kinase, ATP analogue, or phosphatidylinositol 4.5-bisghoshpate revealed that this channel protein has direct effects on cell swelling induced enhancement of slowly activating delayed rectifier K current. It is imortant to analyze the relationship between cell swelling in myocardial damage and KCNQ1 function In clinical medicine, acute myocardial infarction is frequently acompanies fatal dysrhythmias. QT prolongation, ECG change during exercise, and modulation by several drugs are most critical determinants of these dysrhythmias. Hereditary long QT syndrome is a nice model to analyze these factors. K channel anomalies (LQT1 and LQT2) are closely related with specific ECG changes during exercise, and has a possible profound significance to predict sudden death. We found a new mutation in SCN5A sodium channel protein, L1855A, and that induces sodium peak current reduction, and cusses lethal arrhythmia in bradycardia and drug challenge. We also discovered the mechanism how mutation at PIP binding site in KCNJ2 channel expressed dominant negative effect, and caused arrhythmia in patients with Anderson syndrome. To investigate how these disorders in ion channel affect ischemic myocardium causing dysrhythmia is one of the most challenging field

Report

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

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Takenaka K: "Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome."Circulation. 107(6). 838-844 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Makita N: "Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation"Circulation. 106(10). 1269-1274 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Haruna T: "Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated"Circ Res. 91(3). 232-239 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kubota T: "Role of KCNQ1 in the cell swelling-induced enhancement of the slowly activating delayed rectifier K(+) current."Jpn J Physiol. 52(1). 31-39 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai T: "Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia."Circulation. 105(22). 2592-2594 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida H: "Bradycardia-induced long QT syndrome caused by a de novo missense mutation in the S2-S3 inner loop of HERG"Am J Med Genet. 98(4). 348-352 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita F: "Characterization and subcellular localization of KCNQ1 with a heterozygous mutation in the C terminus"J Mol Cell Cardiol. 33(2). 197-207 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kubota T: "Evidence for a single nucleotide polymorphism in the KCNQ1 potassium channel that underlies susceptibility to life-threatening arrhythmias"J Cardiovasc Electrophysiol. 12(11). 1223-1229 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Haruna T: "Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K(ATP) channels in guinea-pig ventricular myocytes"Pflugers Arch. 441(2-3). 200-207 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kono Y: "The properties of the Kir6.1-6.2 tandem channel co-expressed with SUR2A"Pflugers Arch. 440(5). 692-698 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akao M: "Angiotensin II type 1 receptor blockade abolishes K(ATP)channel gene expression in rats with myocardial ischemia"J Mol Cell Caridol. 32(2). 2239-2247 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takenaka K.: "Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome"Circulation. 2003 Feb 18. 107(6). 838-844 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Makita N.: "Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation"Circulation. 2002 Sep 3. 106(10). 1269-1274 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Haruna T.: "Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes"Circ Res.2002 Aug 9. 91(3). 232-239 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kubota T.: "Role of KCNQI in the cell swelling-induced enhancement of the slowly activating delayed rectifier K(+) current"Jpn J Physiol.2002 Feb. 52(1). 31-39 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai T.: "Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia"Circulation. 2002 Jun 4. 105(22). 2592-2594 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida H.: "Bradycardia-induced long QT syndrome caused by a de novo missense mutation in the S2-S3 inner loop of HERG"Am J Med Genet.2001 Feb 1. 98(4). 348-352 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita F.: "Characterization and subcellular localization of KCNQ1 with a heterozygous mutation in the C terminus"J Mol Cell Cardiol.2001 Feb. 33(2). 197-207 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kubota T.: "Evidence for a single nucleotide polymorphism in the KCNQ1 potassium channel that underlies susceptibility to life-threatening arrhythmias"J Cardiovasc Electrophysiol. 12(11). 1223-1229 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Haruna T.: "Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K(ATP) channels in gwnea-pig ventricular myocytes"Pflugers Arch. 2000 Dec. 441(2-3). 200-207 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kono Y.: "The properties of the Kir6.1-6.2 tandem channel coexpressed with SUR2A"Pflugers Arch. 2000 Sep. 440(5). 692-698 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akao M.: "Angiotensin II type 1 receptor blockade abolishes specific KATP channel gene expression in rats with myocardial ischemia"J Mol Cell Caridol 2000. 32(12). 2239-2247 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kubota, T: "Role of KCNQ1 in the cell swelling-induced enhancement of the slowly activating delayed rectifier K(+) current"Jpn. J. Physiol. 52(1). 31-39 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ai, T: "Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmis"Circulation. 105(22). 2592-2594 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Haruna, T: "Alpha1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents"Circ. Res. 91(3). 232-239 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Makita, N: "Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation"Circulation. 106(10). 1269-1274 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takenaka, K: "Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the Long-QT syndrome"Circulation. 107(6). 838-844 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ai T, Fujiyama Y, Otani H, et al.: "Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia"Circulation. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Akao M, Sakurai T, Otani H, et al.: "Angiotensin II type 1 receptor blockade abolishes specific K (ATP) channel gene expression in rats with myocardial ischemia"J Mol Cell Cardiol. 32(12). 2239-2247 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kubota T, Horie M, Otani H, et al.: "Evidence for a single nucleotide polymorphism in the KCNQ1 potassium channel that underlies susceptibility to life-threatening arrhythmias"J Cardiovasc Electrophysiol. 12(11). 1223-1229 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Haruna T, Horie M, Otani H, et al.: "Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K (ATP) channels in guinea-pig ventricular myocytes"Pflugers Arch. 441(2-3). 200-207 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida H, Horie M, Otani H, et al.: "Bradycardia-induced long QT syndrome caused by a de novo missense mutation in the S2-S3 inner loop of HERG"Am J Med Genet. 98(4). 348-352 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamashita F, Horie M, Otani H, et al.: "Charactrerization and subcellular localization of KCNQ1 with a heterozygous mutation in the C terminus"J Moll cell Cardiol. 33(2). 197-207 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kono Y, Horie M, Otani H, et al.: "The properties of the Kir6.1-6.2 tandem channel co-expressed with SUR2A"Pflugers Arch. 440(5). 692-698 (2000)

    • Related Report
      2001 Annual Research Report

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

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