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心筋興奮・伝導の細胞内調節機構

Research Project

Project/Area Number 02257102
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionThe University of Tokyo

Principal Investigator

杉本 恒明  東京大学, 医学部(病), 教授 (60019883)

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)
遠藤 政夫  山形大学, 医学部, 教授 (40004668)
中谷 晴昭  北海道大学, 医学部, 助教授 (60113594)
Project Period (FY) 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥23,600,000 (Direct Cost: ¥23,600,000)
Fiscal Year 1990: ¥23,600,000 (Direct Cost: ¥23,600,000)
KeywordsGタンパク / ムスカリン性Kチャネル / GTP / NDPキナ-ゼ / α受容体 / β受容体 / タンパクリン酸化酵素 / ミトコンドリアDNA遺伝子
Research Abstract

(1)イオンチャンネル調節タンパクとしてのGタンパク:心房筋細胞についてムスカリン性Kチャンネル活性化におけるGTP・GDP交換反応が定量化され,これに対する受容体活性の修飾作用が示された(杉本)。Gタンパク活性化の新しい機構研究のためにNDPキナ-ゼの利用が試みられた(堅田)。低分子Gタンパクであるras遺伝子産物のKチャンネル機能調節が明らかにされつつある(貝淵)。
(2)各種作動物質によるイオンチャンネル調節、心室筋細胞を用い,過酸化脂質,長鎖acylcarnitine,α受容体刺激などの細胞膜電位,並びにK電流,Ca電流に対する効果が検討された(中谷)。αならびにβ受容体刺激時のこれらの電流計の変化が細胞内Ca動態と対比され,その機序が検討されている(遠藤)。また,B1刺激はCa電流を増すほどにはK電流を増さないことが観察された(飯島)。pHやCaの細胞内動態の変化の細胞収縮との関連においての検討も行われている。タンパクリン酸化酵素による活性化機構研究のための精製酵素が血管平滑筋細胞について検討され,心筋での応用が考えられている(今井)。
(3) ミトコンドリアDNA障害と電気的活動異常:刺激伝導障害を伴う心筋症の臨床例において,心筋細胞のATP産生を不能とするようなミトコンドリアDNA遺伝子変異がみられるものがあることが知られた(小沢)。
班員間の研究連携については次の様な進展があった。生化学的解析とパッチクランプなどの電気生理学的手法を結合させての研究の進展(堅田、貝淵、杉本),酵素系、例えばNDPキナ-ゼのGタンパク活性化などの生理的な役割(堅田),Gタンパクやセカンドメッセンジャ-の病態生理学的意義(中谷),タンパクリン酸化酵素の遺伝子工学的手法による大量生産(今井)など。

Report

(1 results)
  • 1990 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] T.Hisada et al.: "Properties of mebrane currents in isolated smooth muscle cells from guinea pig trachea." Pfluegers Arch.416. 151-161 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shimada,T.et al.: "Trimebutine maleate has inhibitory effects on the voltageーdependent Ca^<++> inward current and other membrane currents in intestinal smooth muscle cells." Gastroenterologica Japonica. 25. 175-179 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kurachi,Y.et al.: "Positive cooperability in activation of the cardiac muscarinic K^+ channel by intracellular GTP." Pfluegers Arch.416. 216-218 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nakaya,H.et al.: "Betaーadrenoceptor mediated depolarization of the resting membrane in guinea pig papillary mucles:Changes in intracellular Na,K and Cl activities." Pfluegers Arch.

    • Related Report
      1990 Annual Research Report
  • [Publications] Tohse,N.et al.: "Inhibitory effect mediated by alpha 1ーadrenoceptors on transient outward current in isolated rat ventricular cells." Pfluegers Arch.415. 575-581 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kushida,H.: "The preferential inhibition of alphaー1 over betaーadrenoceptor mediated positive inotropic effect by organic calcium antagonists in the rabbit papillary muscle." Naunyn Schmiedeberg's Arch Pharmacol.341. 206-214 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Iijima,T.et al.: "Differential modulation by beta adrenoceptors of the inward calcium and the delayed rectifier potassium cruuent in single ventricular cells of the guinea pig heart." J.Pharmacol Exp.Ther.254. 142-146 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tung,S.H.et al.: "A Ca^<++> activated and Ma^<++> in vascular smooth muscle:Comparison with plasma membrane Ca^<++> pump ATPase." J.Biochem.

    • Related Report
      1990 Annual Research Report
  • [Publications] Yoshida,Y.et al.: "Two high affinity(Ca^<++> Mg^<++>)ーATPase of vascular smooth muscle plasma membrane preparation:Their relation to the Ca^<++> pumping ATPase." Am.J.Hypertension. 3. 249S-252S (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Imai,S.et al.: "Sarcolemmal(Ca^<++>Mg^<++>)ATPsase of vascular smooth muscle and effects of protein kinase thereupon." J.Biochem.107. 755-761 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kobayashi,I.et al.: "Purification and characterization of five different alpha subunits of guanineーnucleotideーbinding proteins in bovine brain membranes:Their phsiological properties concerning the activities of adenylate cyclase and strial musacirinic K^+ channels." Europ.J.Biochem.191. 499-506 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Maehama,T.et al.: "Botulinum ADPーribosyltransferase activity as affected by detergents and phospholipids." FEBS Letter. 263. 376-380 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Inanobe,A.et al.: "Characterization of four G_p type proteins purified from bovine brain membranes." FEBS Letter. 263. 369-372 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sano,T.et al.: "Effects of antiarrhythmic agents classified as class III group on ischaemiaーinduced myocardial damage in canine hearts." Brit.J.Pharmacol.99. 577-581 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suzuki,H.et al.: "Common protein binding sites in the 5ーflanking regions of human genes for cytochrome Cl and for ubiquinoneーbinding protein." J.Biol.Chem.265. 8159-8163 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ozawa,T.et al.: "Multiple mitochondrial DNA deletions in cardiomyocytes of patients with hypertrophic or dilated cardiomyopathy." Biochem.Biophys.Res.Commun.170. 830-836 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamamoto,T.et al.: "Purification and characterization from bovine brain cytosol of proteins that regulate the GDP/GTP exchange reaction of smg p21s.ras p21ーlike GTP binding proteins." J.Biol.Chem.

    • Related Report
      1990 Annual Research Report
  • [Publications] Fukumoto,Y.et al.: "Activation of the cーfos serum response element by the activated cーHaーras protein in a manner independent of protein kinase C and cAMPーdependent protein kinase." J.Biol.Chem.265. 774-780 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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