• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

心筋イオンチャンネル

Research Project

Project/Area Number 02257107
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionJuntendo University

Principal Investigator

大地 陸男  順天堂大学, 医学部, 教授 (10049025)

Co-Investigator(Kenkyū-buntansha) 三品 昌美  新潟大学, 脳研, 教授 (80144351)
栗山 煕  九州大学, 医学部, 教授 (40037495)
平 則夫  東北大学, 医学部, 教授 (60004553)
亀山 正樹  広島大学, 医学部, 助教授 (60150059)
野間 昭典  九州大学, 医学部, 教授 (00132738)
Project Period (FY) 1990 – 1992
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)
Keywordsカルシウムチャンネル / カリウムチャンネル / ATP / カルパスタチン / 伸展感受性チャンネル / 心筋 / 血管平滑筋 / イオンチャンネル
Research Abstract

心臓の電気活動の電気的素過程、特にイオンチャンネル開閉とその分子的機序を解明し、心臓死の主因をなす不整脈の制御に貢献することが我々の研究目的であった。Caチャンネルについてはパッチクランプ法で単一チャンネル電流が解析され、イソプレナリンがチャンネルの燐酸化により利用率の増大をもたらし、心筋の代謝産物であるアデノシンが、この増大を抑制することが判明した。また、Caチャンネルのrundownを防止する内因性蛋白の同定がクロマトグラフ法とパッチクランプ法で進められ、カルパスタチンと酷似することが判明した。さらに、細胞内Ca濃度がCaチャンネルの制御に影響することがIndoー1を用いてほぼ確認された。リガンド結合実験も行われ、イオン化するジヒドロピリジン(DHP)Ca拮抗薬NKYー722が心筋細胞膜でDHP受容体以外にも結合することが示唆された。Kチャンネルについては、Naーactivated Kチャンネルのコンダクタンスの性質が解明され、細胞内NaやMgによるブロックが判明し、ATPー感受性Kチャンネルについてもニコランジルなどの薬物による修飾も解明された。伸張感受性チャンネルについては、非筋性細胞で詳細な解析を行ったが、心筋にも存在するらしいので同じ手法で研究を行っている。血管平滑筋にいては、門脈平滑筋にATP受容器作動性チャンネルルとATP感受性Kチャンネルが存在した。さらに冠動脈平滑筋にもATP感受性Kチャンルの存在が判明したのでこの研究を行う。チャンネル蛋白の構造機能相関については、ニコチン性アセチルコリン受容体のアミノ基に点変異を導入し、カチオンの選択性に影響する部位を決定した。心筋メッセンジャ-RNAの卵母細胞注入によるチャンネル機能発現の研究が計画している。

Report

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

    (37 results)

All Other

All Publications (37 results)

  • [Publications] R.Ochi: "Modulation of slow gating process of calcium channels by isoprenaline in guineaーpig ventricular cells" Journal of Physiology. 424. 187-204 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Kato: "Mechanism of adenosineーinduced inhibition of calcium channels by isoprenaline in guinea pig ventricular cells" Circulation Research. 67. 1134-1141 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Kameyama: "Intracellular mechanisms involved in “runーdown" of calcium channels" Advance of Experimental Medicine and Biology. 255. 111-118 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Yazawa: "Mechanism of receptorーmediated regulation of the delayed outward potassium current in guineaーpig ventricular myocytes" Journal of Physiology. 421. 135-150 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Yazawa: "An improved method for isolating cardiac myocytes useful for patch clamp studies" Japanese Journal of Physiology. 40. 157-163 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] N.Tohse: "Protein kinase C activation enhances the delayed rectifier potassium current in guinea pig heart" Journal of Molecular and Cellular Cardiology. 22. 725-738 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Tsuji: "The effect of structural modification of several groups on the Dーring of grayanotoxin on its depolarization potency in squid giant axon" The journal of Pharmacology and Experimental Therapeutics.

    • Related Report
      1990 Annual Research Report
  • [Publications] Z.Wang: "Conductance properties of the Na^+ーactivated K^+ channel in guineaーpig ventricular cells" Journal of Physiology.

    • Related Report
      1990 Annual Research Report
  • [Publications] F.M.Tareen: "βーAdrenergic and muscarinic regulation of the chloride current in guineaーpig ventricular cells" Journal of Physiology.

    • Related Report
      1990 Annual Research Report
  • [Publications] D.Qin: "Limitations due to unstirred layers in measuring channel response of excised membrane patch using rapid solution exchange method" Japanese Journal of Physiology.

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Takano: "Selective modulation of the ATPーsensitive K^+ channel by nicorandil in guineaーpig cardiac cell membrane" NaunynーSchmiedeberg's Archiv of Pharmacology. 342. 592-597 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Sokabe: "Electrophysiological analysis of structural aspects of voltageーdependent SR K channel" Comparative Biochemistry.

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Sokabe: "Quantitative videomicroscopy of patch clamped membrames:stress,strain,capacitance,and stretch channel activation" Biophysical Journal.

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Sokabe: "The structure and dynamics of patch clamped membranes:A study by using differential interference light microscopy" Journal of Cell Biology. 111. 599-606 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Nomura: "Aminoglycoside blockade of Ca activated K channel from rat brain synaptosomal membranes incorporated into planar bilayers." Journal of Membrane Biology. 115. 241-251 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] F.Sachs: "Stretch activated ion channels and membrane mechanics" Neuroscience Research. 12. S1-4 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] F.Ito: "Effects of ions and drugs on the responses of sensory axon terminals of decapsulated frog muscle spindles" Neuroscience Research. 12. S15-S26 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Kitamura: "Similarity and diversity of electrical activity in vascular smooth muscles" Progress in Clinical and Biological Research. 327. 257-276 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Okabe: "Actions of cromakalim on ionic currents recorded from single smooth muscle cells of the rat portal vein" The Journal of Pharmacology and Experimental Therapeutics. 252. 832-839 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Inoue: "Endothelin augments unitary calcium chanel currents on the smooth muscle cell membrane of guineaーpig portal vein" Journal of Physiology. 423. 171-191 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Z.Xiong: "ATP activates cationic currents and moduates the Ca current through GTPーbinding protein in rabbit portal vein" Journal of Physiology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Z.Xiong: "Pinacidil inhibits the ryanodineーsensitive outward current and glibenclamide antagonises its action in cells from the rabbit portal vein" British Journal of Pharmacology.

    • Related Report
      1990 Annual Research Report
  • [Publications] M.B.Jackson: "Spontaneous and agonistーinduced openings of an acetylcholine receptor channel composed of bovine muscle αー,βー and δーsubunits" Pflugers Archiv. 417. 129-135 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Sakimura: "Functional expresssion from cloned cDNAs of glutamate receptor species responsive to kainate and quisqualate" FEBS Letters. 272. 73-80 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Mishina: "Structure and function of acetylcholine and glutamate receptors" Fidia Research Foundation Symposium.

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Konno: "Structural determinants of ion selectivity in the acetylcholine receptor channel" Proceedings of the Royal Society of London B.

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Nunoki: "Specific binding sites of NKYー722,a hydrophobic 1,4 dihydropyridine derivative (DHP) in the canine microsomal fractions: comparison with PN 200ー110 binding" Japanese Journal of Pharmacology. 52(Sup). 331 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] N.Nunoki: "Effects of SDー3211,a benzothiazine Ca^<2+> channel blocker on dihydropyridine (DHP) binding to the canine cardiac membrane" Japanese Journal of Physiology. 55(Sup). 91 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] R.Ochi: "Increase in modeー2 sweeps by isoprenaline in cardiac calcium channel treated with BAY K 8644" Japanese Journal of Physiology. 40(Sup). S261 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] R.Ochi: "Modulation of gating process of calcium channel by isoproterenol and nitrendipine in cardiac muscle" Recent Advances in Calcium Channels and Calcium Antagonists.eds.K.Yamada & S.Shibata,Pergamon Press,New York. 11-17 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Kamayama: "Mechanisms of rundown of cardiac calcium channels" Recent Advances in Calcium Channels and Calcium Antagonists.eds.K.Yamada & S.Shibata,Pergamon Press,New York. 3-10 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] A.Noma: "The cardiac ATPーsensitive K^+ channel" Ionic Currents and Ischemia.eds.J.Vereecke,P.P.Bogaert & Verdonck,Leuven University Press,Belgium. 99-119 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Sokabe: "Towards molecular mechanism of the gating in stretch activated channels" Comparative Aspect of Mechanoreception,ed.F.Ito,Springer Verlag.

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Kitamura: "Characteristics of vascular smooth muscle cell membranes and their modifying factors" Coronary Circulation in Physiological and Pathophysiological States,eds.M.Nakamura & P.M.Vanhoutte,Springer Verlag,Tokyo. 125-156 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 三品 昌美: "アセチルコリン受容体の構造と機能" 神経研究の進歩. 34. 911-919 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 崎村 建司: "グルタミン酸受容体チャンネルの構造と機能" 実験医学.

    • Related Report
      1990 Annual Research Report
  • [Publications] 三品 昌美: "分子生物科学 第10巻,神経情報の伝達" 岩波書店, (1991)

    • Related Report
      1990 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi