1991 Fiscal Year Annual Research Report

心筋イオンチャンネル

Research Project

Project/Area Number	03253107
Research Institution	Juntendo 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)
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。

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.
[Publications] Ochi, R.: "Does phosphorylation increase the open probability of calcium channel of cardiac muscle ?" The Physiologist. 34. 102 (1991)
[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)
[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)
[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)
[Publications] 大地陸男: "カルシウム流入の調節" メビオ. 9. 37-42 (1992)
[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.
[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)
[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)
[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)
[Publications] S. Sato: "Antibody to a zinc finger protein in a patient with paraneoplastic cerebellar degeneration." Biochem. Biophys. Res. Commun.178. 198-206 (1991)
[Publications] R. nakano: "Structure of mouse myelin‐associated glycoprotein gene." Biochem. Biophys. Res. Commun.178. 282-290 (1991)
[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)
[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)
[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)
[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)
[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)
[Publications] T.Morita: "Cloning and functional expression of cDNA encoding the mouse β2 subunit of the kainate‐selective glutamate receptor channel." Mol. Brain Res..
[Publications] K. Sakimura: "Primary structure and expression of the γ2 subunit of the glutamate receptoe channel selective for Kainate." Neuron. 8. 267-274 (1992)
[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)
[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)
[Publications] M. Sokabe: "Quantative videomicroscopy of patch clamped membranes:stress.strain.capacitance.and stretch channel activation." Biophys. J.59. 722-728 (1991)
[Publications] M. Sokabe: "Electrophysiological analysis of structural aspects of voltage‐dependent SR K channel." Comp. Biochem. Physiol.98C. 23-30 (1991)
[Publications] K. nomura: "Anion channels from rat brain synaptosomal membranes incorporated into planar bilayers." J. Membr. Biol.124. 53-62 (1991)
[Publications] E. Hasino: "Hair cell damage and recovery following chronic application of kanamycin in the chick cochlea." Hearing Res.52. 356-368 (1991)
[Publications] C.L. Bawman: "Mechanotransducing ion channels in astrocytes." Brain Res..
[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)
[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)
[Publications] Y. Irawan: "Block of sodium channels by tyramine and its analogue (N‐feruloyl tyramine)in frog ventricular myocytes." Jpn. J. Physiol..
[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.
[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)
[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)
[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)
[Publications] F. M. Tareen: "Adrenergic and muscarinic reguration of the chloride current in guinea‐pig ventricular cells." J. Physiol. (Lond.). 440. 225-241 (1991)
[Publications] Z. Wang: "Conductance properties of the Na^+‐activated K^+ channel in guinea‐pig ventricular cells." J. Physiol. (Lond.). 433. 241-257 (1991)
[Publications] A. Noma: "The ATP‐Sensitive K^+ Channel" Jpn. J. Physiol.41. 177-187 (1991)
[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)
[Publications] A. M. Frace: "Cotrol of the hyperpolarization‐activated cation current by external anions in rabbit sino‐atrial node cells." J. .Physiol..(1992)
[Publications] T. Mitsuie: "Exponential of the cardiac Na^+ current in single guinea‐pig ventricular cells." J. Physiol..(1992)
[Publications] K. ono: "Synergistic action of cyclic GMP on catecholamine‐induced chloride current in guinea‐pig ventricular cells." J. Physiol..(1992)
[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)
[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)
[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)
[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)
[Publications] S. Suzuki: "Effects of endothelin‐1 on endothelial cells in the porcine coronary artery." Circuration Research. 69. 1361-1368 (1991)
[Publications] S. Kajioka: "Mechanisms of vasoddilation induced by potassium‐channel activators." Clinical Science. 81. 129-139 (1991)
[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)
[Publications] S. Kajioka: "Guanosine diphosphate activates an adenosine 5'‐triphosphate‐sensitive K^+ channel in the rabbit portal vein." J. physiol.444. 397-418 (1991)
[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)
[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,
[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,
[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,
[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,
[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,
[Publications] K. Kitamura: "Conronary circuration in Physiological and Pathophysiological States" Springerー Verlag, (1991)
[Publications] Z. L. Xiong: "Role of adenosine and adenine nucleotides in the biological system." Elsevier, (1991)

1991 Fiscal Year Annual Research Report

心筋イオンチャンネル

Principal Investigator

大地 陸男 順天堂大学, 医学部, 教授 (10049025)

Research Products

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

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

[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)

[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)

[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)

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

[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.

[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)

[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)

[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)

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

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

[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)

[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)

[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)

[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)

[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)

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

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

[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)

[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)

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

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

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

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

[Publications] C.L. Bawman: "Mechanotransducing ion channels in astrocytes." Brain Res..

[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)

[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)

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

[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.

[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)

[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)

[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)

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

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

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

[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)

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

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

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

[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)

[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)

[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)

[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)

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

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

[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)

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

[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)

[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,

[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,

[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,

[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,

[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,

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

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

大地陸男順天堂大学, 医学部, 教授 (10049025)

[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)

[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)

[Publications] 大地陸男: "カルシウム流入の調節" メビオ. 9. 37-42 (1992)

[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)

[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)

[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)

[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)

[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)

[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)

[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,

[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,

[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,

[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,