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2013 Fiscal Year Final Research Report

Positive feedback mechanism for the regulation of intracellular Ca2+ concentration and related ion channels as novel drug targets

Research Project

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Project/Area Number 23390020
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionNagoya City University

Principal Investigator

IMAIZUMI Yuji  名古屋市立大学, 薬学研究科(研究院), 教授 (60117794)

Co-Investigator(Kenkyū-buntansha) OHYA Susumu  京都薬科大学, 薬学部, 教授 (70275147)
YAMAMURA Hisao  名古屋市立大学, 薬学研究科, 准教授 (80398362)
Co-Investigator(Renkei-kenkyūsha) HIGUCHI Tsunehiko  名古屋市立大学, 薬学研究科, 教授 (50173159)
ASAI Kiyofumi  名古屋市立大学, 医学研究科, 教授 (70212462)
HIRONO Syuichi  北里大学, 薬学部, 教授 (30146328)
Project Period (FY) 2011-11-18 – 2014-03-31
Keywords薬理学 / イオンチャネル / 非興奮性細胞 / カルシウム活性化カリウムチャネル / 正帰還カルシウム制御機構 / 細胞内カルシウム動態 / 発現調節 / ストア作動性カルシウムチャネル
Research Abstract

The present study revealed that, in non-excitable cells such as endothelial cells, lymphocytes, chondrocytes and airway cilliated cell, Ca2+-activated K+ (KCa) channels and store-operated Ca2+ (SOC) channels play significant roles in the positive feedback mechanism for the regulation of intracellular Ca2+ concentration ([Ca2+]i). This [Ca2+]i elevation elicites cellular responses to various types of stimula under physiological conditions or is involved in pathological processes. In brain capillary endothelial cells and chondrocytes, Ca2+-release activated Ca2+ channel is a major component of SOC channels and regulates cell proliferation. In T lymphocytes isolated from inflammatory disease model mice, the change in expression level of intermediate-conductance KCa channel is related to pathological processes. In ciliated cells, ATP-sensitive K+ channel contribute to the positive feedback mechanism for [Ca2+]i, and facilitate ciliary movement and consequently promote airway clearance.

  • Research Products

    (46 results)

All 2014 2013 2012 2011 Other

All Journal Article (23 results) (of which Peer Reviewed: 23 results) Presentation (20 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Spontaneous and nicotine-induced Ca^<2+> oscillations mediated by Ca^<2+> influx in rat pinealocytes2014

    • Author(s)
      Mizutani H, Yamamura H, Muramatsu M, Kiyota K, Nishimura K, Suzuki Y, Ohya S, Imaizumi Y
    • Journal Title

      Am J Physiol Cell Physiol

    • DOI

      10.1152/ajpcell.00014.2014

    • Peer Reviewed
  • [Journal Article] Up-regulation of KCa3.1 K^+ channel in mesenteric lymph node CD4^+ T-lymphocytes from a mouse model of dextran sodium sulfate-induced inflammatory bowel disease2014

    • Author(s)
      Ohya S, Fukuyo Y, Kito H, Shibaoka R, Matsui M, Niguma H, Maeda Y, Yamamura H, Fujii M, Kimura K, Imaizumi Y
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

    • DOI

      10.1152/ajpgi.00156.2013

    • Peer Reviewed
  • [Journal Article] The multiple expression of Ca^<2+>-activated Cl^- channels via homo- and hetero-dimer formation of TMEM16A splicing variants in murine portal vein2014

    • Author(s)
      Ohshiro J, Yamamura H, Saeki T, Suzuki Y, Imaizumi Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 443(2) Pages: 518-23

    • DOI

      10.1016/j.bbrc.2013.11.117

    • Peer Reviewed
  • [Journal Article] Caveolin-1 facilitates the direct coupling between large-conductance Ca^<2+>-activated K^+ (BK_<Ca>) and Cav1.2 Ca^<2+> channels and their clustering to regulate membrane excitability in vascular myocytes2013

    • Author(s)
      Suzuki Y, Yamamura H, Ohya S, Imaizumi Y
    • Journal Title

      J Biol Chem

      Volume: 288(51) Pages: 36750-61

    • DOI

      10.1074/jbc.M113.511485

    • Peer Reviewed
  • [Journal Article] New screening system for selective blockers of voltage-gated K^+ channels using recombinant cell lines dyingupon single action potential2013

    • Author(s)
      Fujii M, Hayashi K, Ohya S, Yamamura H, Imaizumi Y
    • Journal Title

      J Pharmacol Sci

      Volume: 123(2) Pages: 147-58

    • DOI

      10.1254/jphs.13063FP

    • Peer Reviewed
  • [Journal Article] Enhancement of Ca^<2+> influx and ciliary beating by membrane hyperpolarization due to ATP-sensitive K^+ channel opening in mouse airway epithelial cells2013

    • Author(s)
      Ohba T, Sawada E, Suzuki Y, Yamamura H, Ohya S, Tsuda H, Imaizumi Y
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 347(1) Pages: 145-53

    • DOI

      10.1124/jpet.113.205138

    • Peer Reviewed
  • [Journal Article] Overactive bladder mediated by accelerated Ca^<2+> influx mode of Na^+/Ca^<2+> exchanger in smooth muscle2013

    • Author(s)
      Yamamura H, Cole WC, Kita S, Hotta S, Murata H, Suzuki Y, Ohya S, Iwamoto T, Imaizumi Y
    • Journal Title

      Am J Physiol Cell Physiol

      Volume: 305(3) Pages: C299-308

    • DOI

      10.1152/ajpcell.00065.2013

    • Peer Reviewed
  • [Journal Article] Role of the KCa3.1 K^+ channel in auricular lymph node CD4^+ T-lymphocyte function of the delayed-type hypersensitivity model2013

    • Author(s)
      Ohya S, Nakamura E, Horiba S, Kito H, Matsui M, Yamamura H, Imaizumi Y
    • Journal Title

      Br J Pharmacol

      Volume: 169(5) Pages: 1011-23

    • DOI

      10.1111/bph.12215

    • Peer Reviewed
  • [Journal Article] Facilitated hyperpolarization signaling in vascular smooth muscle-overexpressing TRIC-A channels2013

    • Author(s)
      Tao S, Yamazaki D, Komazaki S, Zhao C, Iida T, Kakizawa S, Imaizumi Y, Takeshima H
    • Journal Title

      J Biol Chem

      Volume: 288(22) Pages: 15581-9

    • DOI

      10.1074/jbc.M112.435396

    • Peer Reviewed
  • [Journal Article] Direct molecular interaction ofcaveolin-3 with KCa1.1 channel in living HEK293 cell expression system2013

    • Author(s)
      Suzuki Y, Yamamura H, Ohya S, Imaizumi Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 430(3) Pages: 1169-74

    • DOI

      10.1016/j.bbrc.2012.12.015

    • Peer Reviewed
  • [Journal Article] Total internal reflection fluorescence imaging ofCa^<2+>-induced Ca^<2+> release in mouse urinary bladder smooth muscle cells2012

    • Author(s)
      Yamamura H, Imaizumi Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 427(1) Pages: 54-9

    • DOI

      10.1016/j.bbrc.2012.08.145

    • Peer Reviewed
  • [Journal Article] Down-regulation of the large-conductance Ca^<2+>-activated K^+ channel, KCa1.1 in the prostatic stromal cells of benign prostate hyperplasia2012

    • Author(s)
      Niwa S, Ohya S, Kojima Y, Sasaki S, Yamamura H, Sakuragi M, Kohri K, Imaizumi Y
    • Journal Title

      Biol Pharm Bull

      Volume: 35(5) Pages: 734-44

    • DOI

      10.1248/bpb.35.737

    • Peer Reviewed
  • [Journal Article] Involvement of IP3 formation in thevoltage-dependent regulation of the Ca^<2+> concentration in porcine coronary arterial smooth muscle cells2012

    • Author(s)
      Yamamura H, Ohya S, Muraki K, Imaizumi Y
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 342(2) Pages: 486-96

    • DOI

      10.1124/jpet.112.194233

    • Peer Reviewed
  • [Journal Article] Development of recombinant cell line co-expressing mutated Nav1.5, Kir2.1, and hERG for the safety assay of drug candidates2012

    • Author(s)
      Fuji M, Ohya S, Yamamura H, Imaizumi Y
    • Journal Title

      J Biomol Screen

      Volume: 17(6) Pages: 773-84

    • DOI

      10.1177/1087057112442102

    • Peer Reviewed
  • [Journal Article] Molecular assembly and dynamics of fluorescent protein-tagged single KCa1.1 channel in expression system and vascular smooth muscle cells2012

    • Author(s)
      Yamamura H, Ikeda C, Suzuki Y, Ohya S, Imaizumi Y
    • Journal Title

      Am J Physiol Cell Physiol

      Volume: 302(8) Pages: C1257-68

    • DOI

      10.1152/ajpcell.00191.2011

    • Peer Reviewed
  • [Journal Article] イオンチャネル標的創薬におけるHTSの現状と展望2011

    • Author(s)
      藤井将人, 大矢進, 山村寿男, 今泉祐治
    • Journal Title

      日薬理誌

      Volume: 138(6) Pages: 229-33

    • DOI

      10.1254/fpj.138.229

    • Peer Reviewed
  • [Journal Article] 創薬標的としてのイオンチャネル・トランスポーターの新たな研究法・検索法2011

    • Author(s)
      金子周司, 今泉祐治
    • Journal Title

      日薬理誌

      Volume: 138(6) Pages: 227

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/22303567

    • Peer Reviewed
  • [Journal Article] Serotonin augments gut pacemaker activity via 5-HT3 receptors2011

    • Author(s)
      Liu HN, Ohya S, Nishizawa Y, Sawamura K, Iino S, Syed MM, Goto K, Imaizumi Y, Nakayama S
    • Journal Title

      PLoS One

      Volume: 6(9) Pages: e24928

    • DOI

      10.1371/journal.pone.0024928

    • Peer Reviewed
  • [Journal Article] TRIC-A channels in vascular smooth muscle contribute to blood pressure maintenance2011

    • Author(s)
      Yamazaki D, Tabara Y, Kita S, Hanada H, Komazaki S, Naitou D, Mishima A, Nishi M, Yamamura H, Yamamoto S, Kakizawa S, Miyachi H, Yamamoto S, Miyata T, Kawano Y, Kamide K, Ogihara T, Hata A, Umemura S, Soma M, Takahashi N, Imaizumi Y, Miki T, Iwamoto T, Takeshima H
    • Journal Title

      Cell Metab

      Volume: 14(2) Pages: 231-41

    • DOI

      10.1016/j.cmet.2011.05.011

    • Peer Reviewed
  • [Journal Article] Up-regulation of Kir2.1 by ER stress facilitates cell death of brain capillary endothelial cells2011

    • Author(s)
      Kito H, Yamazaki D, Ohya S, Yamamura H, Asai K, Imaizumi Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 411(2) Pages: 293-8

    • DOI

      10.1016/j.bbrc.2011.06.128

    • Peer Reviewed
  • [Journal Article] Intermediate-conductance Ca^<2+>-activated K^+ channel, KCa3.1, as a novel therapeutic target for benign prostatic hyperplasia2011

    • Author(s)
      Ohya S, Niwa S, Kojima Y, Sasaki S, Sakuragi M, Kohri K, Imaizumi Y
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 338(2) Pages: 528-36

    • DOI

      10.1124/jpet.111.182782

    • Peer Reviewed
  • [Journal Article] Involvement of dominant-negative spliced variants of the intermediate conductance Ca^<2+>-activated K^+ channel, KCa3.1, in immune function of lymphoid cells2011

    • Author(s)
      Ohya S, Niwa S, Yanagi A, Fukuyo Y, Yamamura H, Imaizumi Y
    • Journal Title

      J Biol Chem

      Volume: 286(19) Pages: 16940-52

    • DOI

      10.1074/jbc.M110.184192

    • Peer Reviewed
  • [Journal Article] Contribution of Kir2 potassium channels to ATP-induced cell death in brain capillary endothelial cells and reconstructed HEK293 cell model2011

    • Author(s)
      Yamazaki D, Kito H, Yamamoto S, Ohya S, Yamamura H, Asai K, Imaizumi Y
    • Journal Title

      Am J Physiol Cell Physiol

      Volume: 300(1) Pages: C75-86

    • DOI

      10.1152/ajpcell.00135.2010

    • Peer Reviewed
  • [Presentation] 脳血管内皮細胞の細胞周期進行に対するCARC チャネルの役割2014

    • Author(s)
      鬼頭宏彰, 山村寿男, 鈴木良明, 大矢進, 浅井清文, 今泉祐治
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本
    • Year and Date
      2014-03-30
  • [Presentation] BK チャネル‐VDCC 複合体形成 及び血管平滑筋細胞機能に対する カベオリン1 /カベオラの寄与2014

    • Author(s)
      鈴木良明, 山村寿男, 大矢進, 今泉祐治
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Year and Date
      2014-03-30
  • [Presentation] Na^+/Ca^<2+>交換体の逆回転亢進によって生じる過活動膀胱2014

    • Author(s)
      山村寿男, William C. Cole, 喜多紗斗美, 堀田真吾, 村田秀道, 鈴木良明, 大矢進, 岩本隆宏, 今泉祐治
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Year and Date
      2014-03-30
  • [Presentation] 炎症性腸疾患モデルマウスの腸間膜リンパ節CD^<4+>陽性リンパ球におけるカルシウム活性化カリウムチャネルKCa3.1 活性化機構における機能制御分子の役割2014

    • Author(s)
      柴岡里奈, 松井未来, 福与由香, 仁熊宏樹, 藤井正徳, 山村寿男, 今泉祐治, 大矢進
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Year and Date
      2014-03-28
  • [Presentation] 蛍光ビーズを用いた気道クリアランス評価系の開発2014

    • Author(s)
      大羽輝弥, 澤田英士, 鈴木良明, 山村寿男, 大矢進, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-21
  • [Presentation] 新規BKαスプライスバリアント体によるBK チャネル機能修飾機構の解析2014

    • Author(s)
      鈴木良明, 大矢進, 山村寿男, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-21
  • [Presentation] 門脈圧亢進症モデルマウスの門脈におけるTMEM16A の発現解析2014

    • Author(s)
      近藤 るびい, 大城 隼也, 鈴木 良明, 山村 寿男, 今泉 祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-21
  • [Presentation] マウス門脈において機能発現するTMEM16A スプライスバリアント体の特性2014

    • Author(s)
      大城隼也, 佐伯尚紀, 山村寿男, 鈴木良明, 大矢進, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-21
  • [Presentation] 脳血管内皮細胞におけるCRAC チャネルを介した細胞周期制御機構の解明2014

    • Author(s)
      鬼頭宏彰, 山村寿男, 鈴木良明, 大矢進, 浅井清文, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-21
  • [Presentation] ラット松果体で機能発現するCa^<2+>活性化Cl^-(TMEM16B)チャネル2014

    • Author(s)
      西村歌織, 山村寿男, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-21
  • [Presentation] 男性ホルモンによる大コンダクタンスCa^<2+>活性化K^+チャネル発現制御機構2014

    • Author(s)
      Regis Azizieh, 大野晃稔, 大矢進, 山村寿男, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-20
  • [Presentation] ヒト由来軟骨肉腫細胞株(OUMS-27)におけるCl^-チャネルの分子実体の解明2014

    • Author(s)
      栗田卓, 鈴木良明, 山村寿男, 大矢進, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-20
  • [Presentation] 膀胱平滑筋Na^+/Ca^<2+>交換系の逆回転促進によって起こる過活動膀胱2014

    • Author(s)
      山村寿男, William C. Cole, 喜多紗斗美, 堀田真吾, 村田秀道, 鈴木良明, 大矢進, 岩本隆宏, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-20
  • [Presentation] 腎血管性高血圧モデルマウスにおける腸間膜動脈の血管張力に対する内向き整流性K^+チャネル(Kir2.1)の関与2014

    • Author(s)
      服部美波, 丸山史登, 鈴木良明, 山村寿男, 大矢進, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-19
  • [Presentation] マウス非妊娠・妊娠子宮平滑筋における細胞内Ca^<2+>制御機構機能解析2014

    • Author(s)
      松木克仁, 竹本将士, 鈴木良明, 山村寿男, 大矢進, 竹島浩, 今泉祐治
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-19
  • [Presentation] 脳血管内皮細胞におけるCa^<2+> release-activated Ca^<2+> channel を介した細胞周期制御機構の解明2013

    • Author(s)
      鬼頭宏彰, 山村寿男, 鈴木良明, 大矢進, 浅井清文, 今泉祐治
    • Organizer
      第23回日本循環薬理学会
    • Place of Presentation
      福岡
    • Year and Date
      2013-12-06
  • [Presentation] 平滑筋収縮制御機構におけるCa^<2+>活性化Cl-チャネル(TMEM16A)の役割2013

    • Author(s)
      山村寿男, 邊見智, 大城隼也, 近藤るびい, 鈴木良明, 今泉祐治
    • Organizer
      生理研研究会2013「心血管膜輸送分子の構造・機能・病態の統合的研究戦略」
    • Place of Presentation
      岡崎
    • Year and Date
      2013-11-28
  • [Presentation] 門脈圧亢進症モデルマウスの門脈平滑筋におけるTMEM16A の発現変化2013

    • Author(s)
      近藤るびい, 大城隼也, 鈴木良明, 山村寿男, 今泉祐治
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2013-11-01
  • [Presentation] K_<ATP> チャネル活性化による繊毛運動活性化機構の解明2013

    • Author(s)
      大羽輝弥, 澤田英士, 鈴木良明, 山村寿男, 大矢進, 今泉祐治
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2013-11-01
  • [Presentation] 脳血管内皮細胞における細胞周期進行に対するCRAC チャネルの寄与の解明2013

    • Author(s)
      鬼頭宏彰, 山村寿男, 鈴木良明, 大矢進, 浅井清文, 今泉祐治
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2013-11-01
  • [Book] パートナー薬理学2013

    • Author(s)
      今泉 祐治
    • Total Pages
      69-82
    • Publisher
      南江堂
  • [Remarks]

    • URL

      http://www.phar.nagoya-cu.ac.jp/hp/ysg/

  • [Patent(Industrial Property Rights)] イオンチャネルに作用する化合物のスクリーニング用材料及びその利用2011

    • Inventor(s)
      今泉祐治, 藤井将人, 大矢進, 山村寿男
    • Industrial Property Rights Holder
      公立大学法人名古屋市立大学, 株式会社チャネロサーチテクノロジー
    • Industrial Property Rights Type
      PCT出願
    • Industrial Property Number
      PCT/JP2011/064967
    • Filing Date
      2011-06-29
    • Overseas

URL: 

Published: 2015-06-25  

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