1990 年度実績報告書

心筋興奮・伝導の細胞内調節機構

研究課題

研究課題/領域番号	02257102
研究機関	東京大学
研究代表者	杉本恒明東京大学, 医学部(病), 教授 (60019883)
研究分担者	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)
キーワード	G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
研究概要	(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。

研究成果

(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] T.Hisada et al.: "Properties of mebrane currents in isolated smooth muscle cells from guinea pig trachea." Pfluegers Arch.416. 151-161 (1990)
[文献書誌] 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)
[文献書誌] Kurachi,Y.et al.: "Positive cooperability in activation of the cardiac muscarinic K^+ channel by intracellular GTP." Pfluegers Arch.416. 216-218 (1990)
[文献書誌] 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.
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Tung,S.H.et al.: "A Ca^<++> activated and Ma^<++> in vascular smooth muscle:Comparison with plasma membrane Ca^<++> pump ATPase." J.Biochem.
[文献書誌] 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)
[文献書誌] Imai,S.et al.: "Sarcolemmal(Ca^<++>Mg^<++>)ATPsase of vascular smooth muscle and effects of protein kinase thereupon." J.Biochem.107. 755-761 (1990)
[文献書誌] 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)
[文献書誌] Maehama,T.et al.: "Botulinum ADPーribosyltransferase activity as affected by detergents and phospholipids." FEBS Letter. 263. 376-380 (1990)
[文献書誌] Inanobe,A.et al.: "Characterization of four G_p type proteins purified from bovine brain membranes." FEBS Letter. 263. 369-372 (1990)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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.
[文献書誌] 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)

1990 年度 実績報告書

心筋興奮・伝導の細胞内調節機構

研究代表者

杉本 恒明 東京大学, 医学部(病), 教授 (60019883)

研究成果

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

[文献書誌] 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)

[文献書誌] Kurachi,Y.et al.: "Positive cooperability in activation of the cardiac muscarinic K^+ channel by intracellular GTP." Pfluegers Arch.416. 216-218 (1990)

[文献書誌] 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.

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] Tung,S.H.et al.: "A Ca^<++> activated and Ma^<++> in vascular smooth muscle:Comparison with plasma membrane Ca^<++> pump ATPase." J.Biochem.

[文献書誌] 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)

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

[文献書誌] Maehama,T.et al.: "Botulinum ADPーribosyltransferase activity as affected by detergents and phospholipids." FEBS Letter. 263. 376-380 (1990)

[文献書誌] Inanobe,A.et al.: "Characterization of four G_p type proteins purified from bovine brain membranes." FEBS Letter. 263. 369-372 (1990)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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.

[文献書誌] 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)

1990 年度実績報告書

杉本恒明東京大学, 医学部(病), 教授 (60019883)