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心筋イオンチャンネル

Research Project

Project/Area Number 03253107
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)
野間 昭典  九州大学, 医学部, 教授 (00132738)
亀山 正樹  鹿児島大学, 医学部, 教授 (60150059)
Project Period (FY) 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥22,500,000 (Direct Cost: ¥22,500,000)
Fiscal Year 1991: ¥22,500,000 (Direct Cost: ¥22,500,000)
Keywords心筋 / イオンチャンネル / カルシウムチャンネル / カリウムチャンネル / 塩素チャンネル / 機械受容チャンネル / 血管平滑筋 / クロ-ニング
Research Abstract

心筋のイオンチャンネルの開閉機序、およびその開閉の調節機序を、電気生理学的および分子生物学的に解明することが我々の研究目的であった。(1)Caチャンネル:心房筋の単一チャンネル電流を解析し、βアゴニストがチャンネルの利用率を増大させ、アデノシンのアナログがこの増大を抑制することを明かにした。rundownを防止する細胞内因子を探索する目的で、遺伝子組替え法で作成したカルパスタチンおよびその断片をチャンネルに作用させ、これらにチャンネル活性化作用があることを確認した。細胞内Ca濃度がチャンネルに濃度域の違いにより活性化と不活性化の両現象を示すことをIndo‐1による濃度測定と電流記録を同時に行い明かにした。また、Ca濃度は膜電位を過分極すると減少し、脱分極すると上昇したが、これらの変化はNa/Ca交換機転によるものであった。(2)Naチャンネル:チラミンが心室筋でチャンネルをブロックすることを明らかにした。(3)Kチャンネル:PCR法によりラット心筋よりクロ-ニングした。ラット脳のKチャンネルRC5と類似の遺伝子でコ-ドされ、発現実験で遅延整流性を示すものが得られた。(4)C1チャンネル:βアゴニストの受容体との結合にアルカリ金属が必要なことが判明した。有効性の順序はNa>Li>K,Cs>Tris,TEAであった。(4)機械受容チャンネル:心筋細胞を厚さ100uMのシリコン膜上に培養し、細胞の伸展がチャンネル開孔によって細胞内Ca濃度を上昇させる証拠を得た。(5)血管平滑筋Kチャンネル:開孔薬はGDP存在下に、ATP‐感受性のある小さいコンダクタンスのKチャンネルに作用した。(7)チャンネル蛋白の構造機能相関:AMPA型グルタミン酸受容体チャンネルで、サブユニットの一個のアルギニン残基がイオン透過特性を決定していた。以上のように成果は多い。今後もパッチクランプ法と遺伝子のクロ-ニングにより研究を続ける必要がある。

Report

(1 results)
  • 1991 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Jahnel U.: "Adrenergic effects on calcium channel currents are antagonized by NACA in guinea pig atrial cells." Naunyn‐Schmiedberg's Arch.Pharmacol.

    • Related Report
      1991 Annual Research Report
  • [Publications] Ochi, R.: "Does phosphorylation increase the open probability of calcium channel of cardiac muscle ?" The Physiologist. 34. 102 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Jahnel, U.: "Adrenergic effects on calcium channel currents are antagonized by 5'(N‐ethyl)‐carboxiamido‐ adenosine in guinea‐pig atrial cells." Biophys. J.61. A303 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 大地 陸男,中村 健: "Caチャンネルと興奮・収縮" 病態生理. 10. 423-429 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 大地 陸男: "心筋Caチャンネルの生理的・薬理的調節" 心臓. 24. 206-209 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 大地 陸男: "カルシウム流入の調節" メビオ. 9. 37-42 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] K. Satoh: "The group at C2 of N‐ethylnicotinamide determines the vasodilator potencies and mechanisms of action of nicorandil and its congeners in canine coronary arteries." Naunyn‐Schmiedeberg's Arch. Pharmacol.

    • Related Report
      1991 Annual Research Report
  • [Publications] K. Satoh: "Differential antagonism by glibenclamide of the relaxant effects of cromakalim.pinacidil and nicorandil on canine large coronary arteries." Naunyn‐Schmiedeberg's Arch. Pharmacol.343. 76-82 (1991)

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      1991 Annual Research Report
  • [Publications] H. Yamada: "Comparison of the effects of the novel vasodilator FK409 with those of nitroglycerin in isolated coronary artery of the dog." Br. J. Pharmacol.103. 1713-1718 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T. Konno: "Rings of anionic amino acids as structural determinants of ion selectivity in the acetylcholine receptor channel." Proc. R. Soc. Lond.B244. 69-79 (1991)

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      1991 Annual Research Report
  • [Publications] S. Sato: "Antibody to a zinc finger protein in a patient with paraneoplastic cerebellar degeneration." Biochem. Biophys. Res. Commun.178. 198-206 (1991)

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      1991 Annual Research Report
  • [Publications] R. nakano: "Structure of mouse myelin‐associated glycoprotein gene." Biochem. Biophys. Res. Commun.178. 282-290 (1991)

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      1991 Annual Research Report
  • [Publications] K. Imoto: "A ring of uncharged polar amino acids as a component of channel constriction in the nicotinic acetylcholine receptor." FEBS Lett.289. 193-200 (1991)

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      1991 Annual Research Report
  • [Publications] M. Mishina: "A single amino acid residue determines the Ca^<2+> permeability of AMPA‐selective glutamate receptor channels." Biochem. Biophys. Res. Commun.180. 813-821 (1991)

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      1991 Annual Research Report
  • [Publications] M. Mishina: "Structure and function of acetylcholine and glutamate receptors.in "Neurotransmitter reguletion of gene transcription"" Fidia Rsearch Foundation Symposium. 7. 133-142 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S. Kawamoto: "Functional expression of the α1 subunit of the AMPA‐selective glutamate receptor channel. using a Baculovirus system." Biochem. Biophys. Res. Commun.181. 756-763 (1991)

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      1991 Annual Research Report
  • [Publications] M. Mishina: "Structure and function of the AMPA‐selective glutamate receptor channel." Proceedings of the First Biennial International Conference on Amino Acid Research.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Morita: "Cloning and functional expression of cDNA encoding the mouse β2 subunit of the kainate‐selective glutamate receptor channel." Mol. Brain Res..

    • Related Report
      1991 Annual Research Report
  • [Publications] K. Sakimura: "Primary structure and expression of the γ2 subunit of the glutamate receptoe channel selective for Kainate." Neuron. 8. 267-274 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 三品 昌美: "神経情報伝達の分子機構" 新潟医学会雑誌. 105. 301-303 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 三品 昌美: "分子レベルからみたグルタミン酸受容体チャンネル" 神経研究の進歩. 35. 951-952 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M. Sokabe: "Quantative videomicroscopy of patch clamped membranes:stress.strain.capacitance.and stretch channel activation." Biophys. J.59. 722-728 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M. Sokabe: "Electrophysiological analysis of structural aspects of voltage‐dependent SR K channel." Comp. Biochem. Physiol.98C. 23-30 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K. nomura: "Anion channels from rat brain synaptosomal membranes incorporated into planar bilayers." J. Membr. Biol.124. 53-62 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] E. Hasino: "Hair cell damage and recovery following chronic application of kanamycin in the chick cochlea." Hearing Res.52. 356-368 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] C.L. Bawman: "Mechanotransducing ion channels in astrocytes." Brain Res..

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      1991 Annual Research Report
  • [Publications] 曽我部 正博: "マルチ計測超高倍率顕微鏡の開発。" 比較生理生化学. 8. 22-31 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K. Tuji: "Effect of structural modification of several groups on the D‐ring of grayanotoxin on its depolarization potency in squid giant axon.(1991," J. Phrarmacol. Exp. Ther.257. 788-794 (1991)

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      1991 Annual Research Report
  • [Publications] Y. Irawan: "Block of sodium channels by tyramine and its analogue (N‐feruloyl tyramine)in frog ventricular myocytes." Jpn. J. Physiol..

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      1991 Annual Research Report
  • [Publications] K. Yamaoka: "Ca dependent potentiation of Ca current studied with lndio‐1 in frog ventricular cells." J. Physiol.(Lond.) The Physiological Society.Cambridge meeting.

    • Related Report
      1991 Annual Research Report
  • [Publications] 瀬山 一正: "Na チャンネルと神経毒" 神経研究の進歩. 35. 514-523 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 焼広 益秀: "ナトリウムチャンネルの種類とキネティクス" 膜. 16. 270-276 (1991)

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      1991 Annual Research Report
  • [Publications] A. Noma: "Cytosolic free Ca^<2+> during operation of sodium‐calcium exchange in guinea‐pig heart cells." J. Physiol. (Lond.). 442. 257-276 (1991)

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      1991 Annual Research Report
  • [Publications] F. M. Tareen: "Adrenergic and muscarinic reguration of the chloride current in guinea‐pig ventricular cells." J. Physiol. (Lond.). 440. 225-241 (1991)

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      1991 Annual Research Report
  • [Publications] Z. Wang: "Conductance properties of the Na^+‐activated K^+ channel in guinea‐pig ventricular cells." J. Physiol. (Lond.). 433. 241-257 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] A. Noma: "The ATP‐Sensitive K^+ Channel" Jpn. J. Physiol.41. 177-187 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] D. Oin: "Limitations due to unstirred in measuring channel response of excized membrane patch using rapid solution exchange methods." Jpn. J. Physiol.41. 333-339 (1991)

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      1991 Annual Research Report
  • [Publications] A. M. Frace: "Cotrol of the hyperpolarization‐activated cation current by external anions in rabbit sino‐atrial node cells." J. .Physiol..(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] T. Mitsuie: "Exponential of the cardiac Na^+ current in single guinea‐pig ventricular cells." J. Physiol..(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] K. ono: "Synergistic action of cyclic GMP on catecholamine‐induced chloride current in guinea‐pig ventricular cells." J. Physiol..(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Z. Xiong: "Pinacidil inhibits the ryanodine sensitive outward current and glibenclamide antagonizes its action in cells from the rabbit portal vein." Br. J. Pharmacol.102. 788-790 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Z. Xiong: "ATP activates cationic currents and modulates the calcium current through GTP‐binding protein in rabbit portal vein." J. Physiol. (Lond.). 440. 143-165 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T. Itoh: "Effects of pinacidil on contractile proteins in high K^+‐treated intact, and in β‐escin‐treated skinned smooth muscle of the rabbit mesenteric artery." Br. J. Pharmacol.103. 1697-1702 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S. Ito: "Effects of lemakalim on changes in Ca^<2+> concentration and mechanical activity induced by noradrenaline inthe rabbit mesenteric artery." Br. J. Pharmacol.104. 227-233 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S. Suzuki: "Effects of endothelin‐1 on endothelial cells in the porcine coronary artery." Circuration Research. 69. 1361-1368 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S. Kajioka: "Mechanisms of vasoddilation induced by potassium‐channel activators." Clinical Science. 81. 129-139 (1991)

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      1991 Annual Research Report
  • [Publications] Z. Xiong: "ATP acivates cationic currents and modurates the calcium current through GTP‐binding protein in rabbit portal vein." J. physiol.440. 143-165 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S. Kajioka: "Guanosine diphosphate activates an adenosine 5'‐triphosphate‐sensitive K^+ channel in the rabbit portal vein." J. physiol.444. 397-418 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 亀山 正樹: "Caチャンネルとその調節。" 代謝 臨時増刊号 「シグナル伝達とそのクロスト-ク」. 28. 39-44 (1991)

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      1991 Annual Research Report
  • [Publications] 三品 昌美: "神経情報の伝達 (1991,分子生物科学,10:91ー116)" 岩波書店,

    • Related Report
      1991 Annual Research Report
  • [Publications] 崎村 建司,三品 昌美: "グルタミン酸受容体チャンネルの構造と機能(1991.実験医学,9:579ー584)" 羊土社,

    • Related Report
      1991 Annual Research Report
  • [Publications] M. Sokabe: "Towards molecular mechanism of the gating in stretch activated ion channel.(1992,Comparative Aspects of Mechnoreceptor Systems.:55‐77)" Springerー Verlag,

    • Related Report
      1991 Annual Research Report
  • [Publications] 曽我部 正博: "機械刺激受容チャネルゲ-ティング機構 (1991.ブレインサイイエンス N:202ー223)" 朝倉書店,

    • Related Report
      1991 Annual Research Report
  • [Publications] 野間 昭典: "シグナル伝達路とそのクロスト-ク(1991 代謝,28(臨時増刊号):381ー383)" 中山書店,

    • Related Report
      1991 Annual Research Report
  • [Publications] K. Kitamura: "Conronary circuration in Physiological and Pathophysiological States" Springerー Verlag, (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Z. L. Xiong: "Role of adenosine and adenine nucleotides in the biological system." Elsevier, (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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