1995 Fiscal Year Annual Research Report

致死性不整脈の新しい治療法に対する細胞電気薬理学的アプローチ

Research Project

Project/Area Number	07307025
Research Category	Grant-in-Aid for Co-operative Research (A)
Research Institution	山梨医科大学
Principal Investigator	橋本敬太郎山梨医科大学, 医学部, 教授 (10004665)
Co-Investigator(Kenkyū-buntansha)	木村純子福島県立医科大学, 医学部, 講師 (10186322) 平則夫学位授与機構, 教授 (60004553) 遠藤政夫山形大学, 医学部, 教授 (40004668) 飯島俊彦秋田大学, 医学部, 教授 (30004724) 菅野盛夫北海道大学, 医学部, 教授 (00109422)
Keywords	クラスIII抗不整脈薬 / Kチャネル / Caチャネル / Clチャネル / 筋小胞体 / 細胞内pH / Na・Ca交換 / 心収縮力
Research Abstract	致死性の不整脈が発現し易くなる病態下でイオンチャネル機能の変化、それに影響する細胞内外の環境因子、さらにイオン交換系など、今まで比較的不整脈との関わりで注目されたなかった機能の病態生理学的意義を明らかにさせると共に、病態下にあって致死性不整脈の発現につながる準備状態の機構も明かにすることによって、今までとは異なる概念に立つ薬物による不整脈制御とより有効な治療法を開発することも目的として今年度の研究を行ない、年度末に班会議を行ない情報の交換を行なった。イオンチャネルの実験では単離心筋細胞に対するパッチクランプ法を用いてクラスIIIKチャネル抑制薬の作用を解析すると共に、心筋のα受容体や心筋CIチャネルに対する生体内物質の作用を検討した(北大・菅野、秋田大・飯島、千葉大・中谷、小児医療センター・辻本、名大・児玉)。またKチャネル自身の単離、精製されたものの機能解析を行った。(学位授与機構・平)。またNa・Ca交換系作用薬の作用について検討した(福島医大・木村)。心筋摘出標本を用いた実験では多細胞標本を用いて、筋小胞体の収縮や興奮に対する作用、細胞内pHなどの作用を検討した(山形大・遠藤、熊本大・西)。また生体位心臓での実験では不整脈モデルを作成し、Kチャネル抑制薬の電気生理学的検討を単極性活動電位記録や、マッピング法などを用いて発生機序と、薬物などの影響を検討した(山梨医大・橋本)。

Research Products
(19 results)

All Other

All Publications (19 results)

[Publications] T. Awaji et al.: "Acute antiarrhythmic effects of intravenously administered amiodarone on canine ventricular arrhythmia" Journal of Cardiovascular Pharmacology. 26. 869-878 (1995)
[Publications] Y-X. Xue et al.: "Antiarrhythmic and proarrhythmic effects of sematilide in canine ventricular arrhythmia models" Jpn. J. Pharmacol.70. 129-138 (1996)
[Publications] Y. Hattori et al.: "Inotropic changes induced by fluoroaluminates in rabbit left atrial muscles: Posible involvement of G protein" Brit. J. Pharmacol.114. 224-230 (1995)
[Publications] N. Tohse et al.: "Cyclic GMP-mediated inhibition of L-type Ca^<2+> channel activity by human natriuretic peptide in rabbit heart cells." Brit. J. Pharmacol.114. 1076-1082 (1995)
[Publications] E. Hosoki et al.: "Modulation of cytosoloc Ca^<2+> concentration by thapsigargin and cyclopiazonic acid in human aprtic endothelial cells." Eur. J.Pharmacol.(Mol. Pharmacol. Sec.). 288. 131-137 (1995)
[Publications] H.Watanabe et al.: "L-Type Ca channel block by higyly hydrophilic dihydropyridines in single ventricular cells of guinea-pig hearts." J. Mol. Cell. Cardiol.27. 1271-1279 (1995)
[Publications] M. Ehdoh: "The effects of various drugs on the myocardial inotropic response." Gen. Pharmac.26. 1-31 (1995)
[Publications] H. Okada et al.: "Cloning of a swelling-induced chloride surrent related protein from rabbit heart." Biochimica et Biophysica Acta. 1234. 145-148 (1995)
[Publications] T. Yamagishi et al.: "Antiarrhythmic and bradycardic drugs inhibit currents of cloned K^+ channels, K_<v1.2> and K_<v1.4>" Eur. J.Pharmacol.281. 151-159 (1995)
[Publications] J. Kimura: "Effects of external Mg^<2+> on the Na-Ca exchange current in guinea-pig cardiac myocytes." Annals of New York Academy of Sciences. (in press). (1996)
[Publications] K.Mori et al.: "Anticholinergic effects of class III antiarrhythmic drugs in guinea pig atrial cells." Circulation. 91. 2834-2843 (1995)
[Publications] Y. Hara et al.: "SD-3212, a new class I and IV antiarrhythmic drug: a potent inhibitor of the muscarinic acetylcholine-receptor-operated potassium current in guinea-pig atrial cells." Brit. J. Pharmacol.116. 2750-2756 (1995)
[Publications] I. Kodama et al.: "Mechanical regulation of pacemaking activity in the sinoatrial node: Roles of stretch-sensitive channels and calcium dynamics." Heart Vessels. S9. 212-213 (1995)
[Publications] A. Arai et al.: "Roles of Cl^- channels and Ca^<2+> mobilization in the stretchinduced increase of SA mode pacemaker activity." Am. J. Physiol.(in press). (1996)
[Publications] K. Shibata et al.: "KMD-3213, a novel, potent, α_<1a>-adrenoceptor-selective antagonist: Characterization using recombinant human α_1-adrenoceptors and native tissues." Mol. Pharmacol.48. 250-258 (1995)
[Publications] K. Horie. et al.: "Hamster α_<1B>-adrenergic receptor directly activates G_s in the transfected Chinese hamster ovary cells." Mol. Pharmacol.48. 392-400 (1995)
[Publications] Z-S. Lai: "Possible involvement of activation of Cl^--HCO_3^- exchange during simulated ischemia in isolated guinea pig ventricular papillary muscle in vitro." J. Cardiovasc. Pharmacol.(in press). (1996)
[Publications] N.Tokutomi: "Rhythmic Cl-current and physiological roles of the intestinal c-kit-positive cells." Pflueger Arch.431. 169-177 (1995)
[Publications] M. Ehdoh: "New Horizons for Failing Heart Syndrome" Springer-Verlag Tokyo, 187-208 (1996)

1995 Fiscal Year Annual Research Report

致死性不整脈の新しい治療法に対する細胞電気薬理学的アプローチ

Principal Investigator

橋本 敬太郎 山梨医科大学, 医学部, 教授 (10004665)

Research Products

[Publications] T. Awaji et al.: "Acute antiarrhythmic effects of intravenously administered amiodarone on canine ventricular arrhythmia" Journal of Cardiovascular Pharmacology. 26. 869-878 (1995)

[Publications] Y-X. Xue et al.: "Antiarrhythmic and proarrhythmic effects of sematilide in canine ventricular arrhythmia models" Jpn. J. Pharmacol.70. 129-138 (1996)

[Publications] Y. Hattori et al.: "Inotropic changes induced by fluoroaluminates in rabbit left atrial muscles: Posible involvement of G protein" Brit. J. Pharmacol.114. 224-230 (1995)

[Publications] N. Tohse et al.: "Cyclic GMP-mediated inhibition of L-type Ca^<2+> channel activity by human natriuretic peptide in rabbit heart cells." Brit. J. Pharmacol.114. 1076-1082 (1995)

[Publications] E. Hosoki et al.: "Modulation of cytosoloc Ca^<2+> concentration by thapsigargin and cyclopiazonic acid in human aprtic endothelial cells." Eur. J.Pharmacol.(Mol. Pharmacol. Sec.). 288. 131-137 (1995)

[Publications] H.Watanabe et al.: "L-Type Ca channel block by higyly hydrophilic dihydropyridines in single ventricular cells of guinea-pig hearts." J. Mol. Cell. Cardiol.27. 1271-1279 (1995)

[Publications] M. Ehdoh: "The effects of various drugs on the myocardial inotropic response." Gen. Pharmac.26. 1-31 (1995)

[Publications] H. Okada et al.: "Cloning of a swelling-induced chloride surrent related protein from rabbit heart." Biochimica et Biophysica Acta. 1234. 145-148 (1995)

[Publications] T. Yamagishi et al.: "Antiarrhythmic and bradycardic drugs inhibit currents of cloned K^+ channels, K_<v1.2> and K_<v1.4>" Eur. J.Pharmacol.281. 151-159 (1995)

[Publications] J. Kimura: "Effects of external Mg^<2+> on the Na-Ca exchange current in guinea-pig cardiac myocytes." Annals of New York Academy of Sciences. (in press). (1996)

[Publications] K.Mori et al.: "Anticholinergic effects of class III antiarrhythmic drugs in guinea pig atrial cells." Circulation. 91. 2834-2843 (1995)

[Publications] Y. Hara et al.: "SD-3212, a new class I and IV antiarrhythmic drug: a potent inhibitor of the muscarinic acetylcholine-receptor-operated potassium current in guinea-pig atrial cells." Brit. J. Pharmacol.116. 2750-2756 (1995)

[Publications] I. Kodama et al.: "Mechanical regulation of pacemaking activity in the sinoatrial node: Roles of stretch-sensitive channels and calcium dynamics." Heart Vessels. S9. 212-213 (1995)

[Publications] A. Arai et al.: "Roles of Cl^- channels and Ca^<2+> mobilization in the stretchinduced increase of SA mode pacemaker activity." Am. J. Physiol.(in press). (1996)

[Publications] K. Shibata et al.: "KMD-3213, a novel, potent, α_<1a>-adrenoceptor-selective antagonist: Characterization using recombinant human α_1-adrenoceptors and native tissues." Mol. Pharmacol.48. 250-258 (1995)

[Publications] K. Horie. et al.: "Hamster α_<1B>-adrenergic receptor directly activates G_s in the transfected Chinese hamster ovary cells." Mol. Pharmacol.48. 392-400 (1995)

[Publications] Z-S. Lai: "Possible involvement of activation of Cl^--HCO_3^- exchange during simulated ischemia in isolated guinea pig ventricular papillary muscle in vitro." J. Cardiovasc. Pharmacol.(in press). (1996)

[Publications] N.Tokutomi: "Rhythmic Cl-current and physiological roles of the intestinal c-kit-positive cells." Pflueger Arch.431. 169-177 (1995)

[Publications] M. Ehdoh: "New Horizons for Failing Heart Syndrome" Springer-Verlag Tokyo, 187-208 (1996)

橋本敬太郎山梨医科大学, 医学部, 教授 (10004665)