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心筋興奮・伝導の細胞内調節機構

Research Project

Project/Area Number 04248103
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionNagoya University

Principal Investigator

小澤 高将  名古屋大学, 医学部, 教授 (80022771)

Co-Investigator(Kenkyū-buntansha) 堅田 利明  東京工業大学, 生命理工学部, 教授 (10088859)
今井 昭一  新潟大学, 医学部, 教授 (60013869)
飯島 俊彦  秋田大学, 医学部, 教授 (30004724)
中谷 晴昭  千葉大学, 医学部, 教授 (60113594)
遠藤 政夫  山形大学, 医学部, 教授 (40004668)
Project Period (FY) 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥22,500,000 (Direct Cost: ¥22,500,000)
Fiscal Year 1992: ¥22,500,000 (Direct Cost: ¥22,500,000)
Keywords心筋 / 不整派 / c-fos遺伝子 / Cキナーゼ / フォスファチジルイノシトール / カリウムチャネル / フリーラジカル / ミトコンドリアDNA
Research Abstract

心筋の興奮と伝導は、ホルモンなどによって種々に修飾される一方、細胞内のCa濃度や代謝によって調節されている。その破綻は心筋興奮・伝導の異常としての不整派に繋がる。本研究では、これらの細胞内調節の分子機構の解明をめざした。堅田らは細胞膜を介する情報伝達系において、受容体、G蛋白、効果器系分子間の相互作用を制御する蛋白性補助因子の分離精製に成功した。貝淵は、心筋興奮におけるプロテインキナーゼC系の関与を解明するために、c-fos遺伝子の発現制御機構を、Cキナーゼ系やAキナーゼ系とras p21やraf遺伝子産物との相互関係において明らかにした。中谷らは、単離心筋細胞の細胞内潅流しながら、パッチ電極法により膜電流を、イオン選択性微小電極により細胞内pHを記録した。α受容体刺激時のCキナーゼ活性化による変化と、心筋細胞のAキナーゼ系あるいはtyrosine kinase系を刺激した時の変化の相違を明らかにした。遠藤らは、α受容体刺激による心筋電気現象のイオン機序と両者の間に介在する分子機構を解明するために、α受容体サブタイプの機能調節をフォスファチジルイノシトール代謝回転との因果関係の点から明らかにした。飯島らはβ受容体刺激時の強心効果に関連したKチャネルの役割を明らかにした。今井らはcyclic GMP/G-kinaseによる燐酸化の基質と考えられる蛋白を精製し、Ca-ATPase活性化における意義を検討した。中谷らは、フリーラジカルと不整派発生の関連に注目し、細胞内代謝産物として脂肪酸中間代謝産物の心筋の電流系に対する影響を検討した。小澤らは、ミトコンドリアDNAの変異による心筋細胞エネルギー障害と不整派の相関を解明するため、ミトコンドリア遺伝子の酸化的DNA障害について解析し、これと、点変異ならびに欠失などの変異の蓄積との関連を明らかにした。

Report

(1 results)
  • 1992 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] M.Endou: "Electrophysiologic mechanisms responsible for inotropic responses to ketamine in guinea pig and rat myocardium." Anesthesiology. 76. 409-18 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Nakaya: "Electrophysiologic and anticholinergic effects of pirmenol enantiomers in guinea-pig myocardium." Naunyn Schmiedebergs Arch Pharmacol. 346. 555-62 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Nakaya: "Voltage-dependent modification of Vmax recovery from use-dependent block by permenol in guinea pig papillary muscles:comparison with other class I drugs." J Cardiovasc Pharmacol. 19. 140-7 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Nakaya: "Mechanism of the membrane depolarization induced by oxidative stress in guinea-pig ventricular cells." J Mol Cell Cardiol. 24. 523-34 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Shida: "Effects of Cl-channel blockers on beta-adrenoceptor-mediated decreases in resting potential and intracellular Cl-activity in guinea-pig heart." Eur J Pharmacol. 212. 267-70 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Tohse: "Alpha 1-adrenoceptor stimulation enhances the delayed rectifier K+ current of guinea pig ventricular cells through the activation of protein kinase C." Circ Res. 71. 1441-6 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Hayakawa: "Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts." Biochem Biophys Res Commun. 189. 979-85 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Ito: "Mitochondrial DNA mutations in cardiomyopathy." Jpn Circ J. 56. 1045-53 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Torii: "Ageng-associated deletions of human diaphragmatic mitochondrial DNA." Am J Respir Cell Mol Biol. 6. 543-9 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Katayama: "Deleted mitochondrial DNA in the skeletal muscle of aged individuals." Biochem int. 25. 47-56 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Ozawa: "Mitochondrial DNA mutations and disturbances of energy metabolism in myocardium." Jpn Circ J. 55. 1158-64 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Sugiyama: "Quantitative analysis of age-associated accumulation of mitochondrial DNA with deletion in human hearts." Biochem Biophys Res Commun. 180. 894-9 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Adachi: "Induction of smg p21/rap1Ap21/krev-1p21 gene expression during phorbol ester-induced differentiation of a human megakaryocytic leukemia cell line." Oncogene. 7. 323-9 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Ando: "Post-translational processing of rac p21s is important both for their interaction with the GDP/GTP exchange proteins and for their activation of NADPH oxidase." J Biol Chem. 267. 25709-13 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Fujioka: "Transforming and c-fos promoter/enhancer-stimulating activities of a stimulatory GDP/GTP exchange protein for small GTP-binding proteins." J Biol Chem. 267. 926-30 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Hiraoka: "Both stimulatory and inhibitory GDP/GTP exchange proteins,smg GDS and rho GDI,are active on multiple small GTP-binding proteins." Biochem Biophys Res Commun. 182. 921-30 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Hirata: "Involvement of rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle contraction." J Biol Chem. 267. 8719-22 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Horiuchi: "The posttranslational processing of ras p21 is critical for its stimulation of yeast adenylate cyclase." Mol Cell Biol. 12. 4515-20 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Kikuchi: "Molecular cloning of the human cDNA for a stimulatory GDP/GTP exchange protein for C-Ki-ras p21 and smg p21." Oncogene. 7. 289-93 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Miura: "Phosphorylation of smg p21B/rap1Bp21 by cyclic GMP-dependent protein kinase." Febs Lett. 297. 171-4 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Mizuno: "Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins." J Biol Chem. 267. 10215-8 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Muramatsu: "Protein kinase C mutants in the auto-inhibitory region exhibit two distinct properties." Febs Lett. 311. 75-9 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Sakoda: "smg/rap1/Krev-1p21s inhibit the signal pathway to the c-fos promoter/enhancer from c-Ki-ras p21 but not from c-raf-1 kinase in NIH3T3 cells." Oncogene. 7. 1705-11 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Shirataki: "A possible target protein for smg-25A/rab3A small GTP-binding protein." J Biol Chem. 267. 10946-9 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Takai: "Small GTP-binding proteins." Int Rev Cytol. 133. 187-230 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Chiba: "The primary structure of the alpha subunit of a starfish guanosine-nucleotide-binding regulatory protein in volved in 1-methyladenine-induced oocyte maturation." Eur J Biochem. 207. 833-8 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Iiri: "Modification of the function of pertussis toxin substrate GTP-binding protein by cholera toxin-catalyzed ADP-ribosylation." J Biol Chem. 267. 1020-6 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Ito: "On the mechanism of G protein beta gamma subunit activation of the muscarinic K+ channel in guinea pig atrial cell membrane. Comparison with the ATP-sensitive K+ channel." J Gen Physiol. 99. 961-83 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.kanaho: "A protein kinase C inhibitor,staurosporine,Activates phospholipase Dvi a pertussis toxin-sensitive GTP-binding protein in rabbit peritoneal nertrophils." J Biol Chem. 267. 23554-9 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Kontani: "Molecular heterogeneity of the beta gamma-subunits of GTP-binding proteins in bovine brain membranes." Arch Biochem Biophys. 294. 527-33 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Tadenuma: "Properties of 1-methyladenine receptors in starfish oocyte membranes:involvement of pertussis toxin-sensitive GTP-binding protein in the receptor-mediated signal transduction." Biochem Biophys Res Commun. 186. 114-21 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Takei: "A GTP-bindin protein in rat liver nuclei serving as the specific substrate of pertussis toxin-catalyzed ADP-ribosylation." J Biol Chem. 267. 5085-9 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Yamamoto: "Direct activation of purified Go-type GTP binding protein by tricyclic antidepressants." Neurosci Lett. 139. 194-6 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] W.Sato: "Deletion of mitochondrial DNA in patient with conduction block" Am Heart J. 125. 550-552 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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