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Molecular and Applied Pharmacology of Subunits of Ion Channels as Biosensors

Research Project

Project/Area Number 10559002
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field 広領域
Research InstitutionTohoku University

Principal Investigator

YANAGISAWA Teruyuki  Sch.Med., Dept.Pharmacol., Tohoku University, Professor, 大学院・医学系研究科, 教授 (90133941)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Manabu  Sch.Med., Dept.Pharmacol., Tohoku University, Res. Associate, 大学院・医学系研究科, 助手 (80302090)
SUKEGAWA Jun  Sch.Med., Dept.Pharmacol., Tohoku University, Lecturer, 大学院・医学系研究科, 講師 (30187687)
NUNOKI Kazuo  Sch.Med., Dept.Pharmacol., Tohoku University, Lecturer, 大学院・医学系研究科, 講師 (10172743)
MATSUE Tomokazu  Sch.Eng., Dept.Biomol., Tohoku University, Professor, 大学院・工学研究科, 教授 (70173797)
KOBAYASHI Nagao  Sch.Sci., Dept.Chem., Tohoku University, Professor, 大学院・理学研究科, 教授 (60124575)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥6,600,000 (Direct Cost: ¥6,600,000)
KeywordsK^+ channels / Ca^<2+> chanels / Inactivation / Adaptation / Knockout mouse / Dihydropyridine / Salt-sensitive hypertension / K^+チャネル / Ca^<2+>チャネル / サブユニット / 遺伝子改変動物 / チャネル遮断機序 / 食塩感受性高血圧 / 電位依存性カリウムチャネル / 遺伝子改変 / 核膜孔蛋白質 / Znフィンガードメイン / 電位依存性カルシウムチャネル / 高血圧
Research Abstract

N-type inactivation of rat Kv1.4 channels with one, two, or four inactivation balls was investigated using homogeneous populations of channels expressed in Xenopus oocytes. Tandem dimeric and tetrameric constructs of Kv1.4 were made. Channels encoded by tandem cDNAs Kv1.4-Kv1.4Delta1-145 and Kv1.4-[Kv1.4Delta1-145] (3) have two or only one tethered inactivation ball, respectively, whereas Kv1.4 itself encodes channels having four inactivation balls. The time constants for inactivation of macroscopic currents were increased significantly as the number of inactivation balls was decreased, whereas the time constants for recovery from inactivation were not modified. The ratios of the rate constants of inactivation (k (inact) ) of Kv1.4-Kv1.4Delta1-145 and Kv1.4-[Kv1.4Delta1-145] (3) channels to that of the Kv1.4 channel were 0.65 and 0.4, respectively, whereas the ratios of the rate constant of recovery (k (rec) ) of these channels to that of Kv1.4 were almost unity. The rate constants k ( … More inact) for channels having two and four inactivation balls are smaller than those that would be expected if inactivation balls on each channel are independent, suggesting some interaction occurs between inactivation balls. Furthermore, noninactivating current became apparent as the number of inactivation balls on a channel was decreased.
Voltage-dependent calcium channels are crucially important for calcitum influx and following smooth muscle contraction. Beta subunits of these channels are known to modify calcium currerns through pore-forming alfa1 subunits. Among four reported independent beta subunit, the beta3 subunit in cardiovascular system, we have analyzed beta3-null mice. Electrophysiological examinations proved the existence of dihydropyridine (DHP)-sensitive, L-type calcium channels in the smooth muscle cell. Beta3-null mice show no apparent changes in smooth muscle contraction and sensitivity to DHP, and normal blood pressure when they are raised on a normal diet, but the beta3 subunit deficient mice show elevated blood pressure in response to a high-salt diet, with significant reductions in plasma catecholamine concentration. Our finding strongly suggests the adaptation to the null mutation of calcium channel beta subunit results in salt-sensitive hypertension. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Hashimoto Y.,...,Yanagisawa T.: "Changes in the inactivation of rat Kv1.4 K^+ channels induced by varying the number of inactivation particles."J.Biol.Chem.. 275(13). 9358-9362 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami M.,...,Yanagisawa T.: "Antinociceptive effect of cilnidipine, a novel N-type calcium channel antagonist."Brain Res.. 868(1). 123-127 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami,M.,...,Yanagisawa,T.: "Conserved smooth muscle contractility and blood pressure increase in response to high salt diet, in mice lacking β3 subuint of the voltage-dependent calcium channel."J.Cardiovasc.Pharmacol.. 36(Suppl.). S69-S73 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanagisawa,T. et al.: "Selectivity and potency of agonists at the three subtypes of cloned human beta-adrenoceptors expressed in Chinese hamster ovary cells."Tohoku J.Exp.Med.. 192(3). 181-193 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Tsunoda.,...,T.Yanagisawa, et al.: "Determination of catecholamines and their 3-O-methyl metabolites in mouse plasma."Biomed.Chromatogr.. 15. 41-44 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柳澤輝行,布木和夫,村上学: "カルシウムチャネルの分子薬理学"Clinical Calcium. 10・8. 55-59 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 村上学,柳澤輝行 他: "カルシウムチャネルbeta3サブユニット欠損マウスにおける疼痛の検討、オピオイドの基礎と臨床"ミクス社. 176-182(238) (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohuchi Y., Nanai K., Sakurai E., Fikui H., Yanagiswa T., and Watanabe T.: "Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors : A relationship between its sensitivity and the density of H1 receptors."Intern.J.Mol.Med.. 1. 355-360 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugai K., Yanagisawa T., Motohashi O., Suzuki M., and Yoshimoto T.: "Levcromakalim decreases cytoplasmic Ca^<2+>, vascular tone and Ca^<2+> sensitivity in canine basilar artery."Fund.Clin.Pharmacol.. 12. 403-405 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugai K., Yanagisawa T., Motohashi O., Suzuki M., and Yoshimoto T.: "Levcromakalim decreases cytoplasmic Ca^<2+>, and vascular tone in canine basilar artery of SAH model."J.Cardiovasc.Pharmacol.. 33. 868-875 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto Y., Nunoki K., Kudo H., Ishii K., Taira N.and Yanagisawa T.: "Changes in the inactivation of rat Kv1.4 K^+ channels induced by varying the number of inactivation particles."J.Biol.Chem.. 275(13). 9358-9362 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami M., Nakagawasai O., Fujii S., Hosono M., Hozumi S., Esashi A., Taniguchi R., Okamura T., Suzuki T., Sasano H., Yanagisawa T., Tan-No K., Tadano T.Kitamura K.and Kisara K.: "Antinociceptive effect of cilnidipine, a novel N-type calcium channel antagonist."Brain Res.. 868(1). 123-127 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami M., Yamamura S., Fujii S., Murakami A., Okamura T., Nunoki K., Mitui-Saito M., Muraki K., Hano T., Imaizumi Y., Flockerzi V.and Yanagisawa T.: "Conserved smooth muscle contractility and blood pressure increase in response to high salt diet, in mice lacking β3 subuint of the voltage-dependent calcium channel."J.Cardiovasc.Pharmacol.. 36 (Suppl.). S69-S73 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanagisawa T., Satoh T., Yamada, H., Sukegawa J.and Nunoki K.: "Selectivity and potency of agonists for the three subtypes of cloned human β-adrenoceptors expressed in Chinese hamster ovary cells."Thohoku J.Exp.Med.. 192(3). 181-193 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsunoda M., Takezawa K., Yanagisawa T., Kato M.and Imai K.: "Determination of catecholamines and their 3-O-methyl metabolites in mouse plasma."Biomed.Chromatogr.. 15. 41-44 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hashimoto Y.,...,Yanagisawa T.: "Changes in the inactivation of rat Kv1.4 K^+ channels induced by varying the number of inactivation particles."J.Biol.Chem.. 275(13). 9358-9362 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murakami M.,...,Yanagisawa T.: "Antinociceptive effect of cilnidipine, a novel N-type calcium channel antagonist."Brain Res.. 868(1). 123-127 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murakami,M.,...,Yanagisawa,T.: "Conserved smooth muscle contractility and blood pressure increase in response to high salt diet, in mice lacking β3 subuint of the voltage-dependent calcium channel."J.Cardiovasc.Pharmacol.. 36(Suppl.). S69-S73 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yanagisawa,T. et al.: "Selectivity and potency of agonists at the three subtypes of cloned human beta-adrenoceptors expressed in Chinese hamster ovary cells."Tohoku J.Exp.Med.. 192(3). 181-193 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Tsunoda.,...,T.Yanagisawa, et al.: "Determination of catecholamines and their3-O-methyl metabolites in mouse plasma."Biomed.Chromatogr.. 15. 41-44 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 柳澤輝行,布木和夫,村上学: "カルシウムチャネルの分子薬理学"Clinical Calcium. 10・8. 55-59 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 村上学,柳澤輝行 他: "カルシウムチャネルbeta3サブユニット欠損マウスにおける疼痛の検討、オピオイドの基礎と臨床"ミクス社. 176-182(238) (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sugai K.,Yanagisawa Y. et al.: "Levcromakalim decreases cytoplasmic Ca^<2+> and vascular tone in canine basilar artery of SAH model"J. Candiorasc. Pharmacol. 33. 868-875 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasukawa T.Uchida I.,Matue T.: "Microamperometric measurements of photosynthetic activity in a single algal protoplast"Biophysical J.. 76(2). 1129-1135 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hashimoto Y.,Nunoki K. et al.: "Changes in the inactivation of rat Kv1.4 K^+ channels induced by varying the number of inactivation particles"J. Biol. Chem.. 275. in press (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Murakami M. et al.: "Conserved smooth muscle contractility and blood pressure increase in responsts high salt diet, in mice lacking β3 subsist of the Ca^<2+> channels"J. Candiovase. Pharmacol.. in press

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe T.,Sukegawa J. et al.: "A 127-kDa Protein (UV-DDB) binds to the Cytoplasmic Domain of the Alzheimer's Amyloid Precursor Protein"J. Neurochem.. 72. 549-556 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Haraguchi T. et al.: "Live fluorescence imaging reveals early recruitment of emerin, LBR, RanBP2, and Nup153 to reforming functional nuclear envelopes"J. Cell. Sci.. 113. 779-794 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 柳澤 輝行: "新率理学入門(改訂3刷)"南山蛍. 372 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 柳澤 輝行: "KEY WORD 1999-2000 高血圧"先端医学者. 2 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohuchi Y.,Yanai,K.et al.: "Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors." Intern.J.Mol.Med.1. 355-360 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sugai K.,Yanagisawa T.et al.: "Levcromakalim decreases cytoplasmic Ca^<2+>,vascular tone and Ca^<2+> sensitivity in canine basilar artery." Fundam.Clin.Pharmacol.12. 403-410 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sugai K.,Yanagisawa T.et al.: "Levcromakalim decreases cytoplasmic Ca^<2+>and vascular tone in canine basilar artery of SAH model." J.Cardiovasc.Pharmacol.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasukawa,T.,Uchida I.,Matsue T.: "Permeation of redox species through a cell membrane of a single,living Algal protoplast studied by microamperometry" Biochim.Biophys.Acta. 1369. 152-158 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 柳澤輝行、布木和夫: "血管のKチャネル、その2 K_<Ca>とK_Vの分子薬理学." 血管と内皮. 8(2). 186-190 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi N,Nevin W.A.: "Optically active tetrapyrazinoporphyrazines and their circular dichroism in monomeric and dimeric forms." Chem.Lett.851-852 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 柳澤輝行、布木和夫、村上学: "目で見る循環器病シリーズ14 薬物療法 斎藤宗靖(編)" メジカルビュー社、東京, 12 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 柳澤輝行、布木和夫、谷内一彦: "新薬理学入門 (第2刷) 柳澤輝行(編著)" 南山堂, 372 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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