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Endocytosis of human K channel by receptor activation and its intracellular mechanisms

Research Project

Project/Area Number 22590235
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionYamagata University

Principal Investigator

ISHII Kuniaki  山形大学, 医学部, 教授 (10184459)

Co-Investigator(Kenkyū-buntansha) YAMAZAKI Yoshihiko  山形大学, 医学部, 准教授 (10361247)
蔦川 修生  山形大学, 医学部, 助教 (00551855)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords電位依存性 Kチャネル / エンドサイトーシス / 受容体 / 電位依存性Kチャネル / チャネル / シグナル情報伝達系
Research Abstract

The slowly activating delayed rectifier K^+ channel (IKs channel) is composed of KCNQ1 and KCNE1 subunits. The present study was designed to investigate whether activation of Gq protein-coupled receptor (GqPCR) caused endocytosis of the I_<Ks> channel.
1. Effects of GqPCR activation on localization of the pore-forming subunit KCNQ1 were investigated by confocal laser scanning microscopy. It was suggested that AT_1R activation resulted in endocytosis of KCNQ1.
2. AT_1R-induced endocytosis of KCNQ1 was clathrin-dependent, where PKC activation was involved. Ubiquitination of KCNQ1 seemed to have nothing to do with the endocytosis.
3. Activation of α_<1A> and α_<1B> receptor obviously caused endocytosis of KCNQ1. Although AR_<α1>-induced endocytosis of KCNQ1 was clathrin-dependent, it did not require PKC activation in contrast to AT_1R. Involvement of ubiquitination of KCNQ1 was suggested.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (43 results)

All 2013 2012 2011 2010 Other

All Journal Article (10 results) (of which Peer Reviewed: 9 results) Presentation (31 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Is a Novel <i>SCN3B</i> Mutation Commonly Found in <i>SCN5A</i>-Negative Brugada Syndrome Patients?2013

    • Author(s)
      Kurakami K, Ishii K.
    • Journal Title

      Circulation Journal

      Volume: 77 Issue: 4 Pages: 900-901

    • DOI

      10.1253/circj.CJ-13-0242

    • NAID

      10031138988

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] G_<αh>/transglutaminase-2 activity is required for maximal activatio of adenylylcyclase 8 in human and rat g(n) lioma cells2013

    • Author(s)
      Obara Y, Yanagihata Y, Abe T, Dafik L, Ishii K, Nakahata N.
    • Journal Title

      Cell Signal

      Volume: 25 Issue: 3 Pages: 589-597

    • DOI

      10.1016/j.cellsig.2012.11.021

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endocytic Regulation of Voltage-Dependent Potassium Channels in the Heart2012

    • Author(s)
      Ishii K, Norota I, Obara Y.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 120 Issue: 4 Pages: 264-269

    • DOI

      10.1254/jphs.12R12CP

    • NAID

      10031147574

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of inositol 1, 4, 5-trisphosp hate receptors during preconditioning low-f requency stimulation leads to reversal of L TP in hippocampal CA1 neurons2012

    • Author(s)
      Yamazaki Y, Fujii S, Aihara T, Mikoshiba K.
    • Journal Title

      Neurosci

      Volume: 207 Pages: 1-11

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] NMDA receptor-mediated Ca(2+) influx triggers nucleocytoplasmic translocation of diacylglycerol kinase ζ under oxygen-glucose deprivation conditions, an in vitro model of ischemia, in rat hippocampal slices2012

    • Author(s)
      Suzuki Y, Yamazaki Y, Hozumi Y, Okada M, Tanaka T, Iseki K, Ohta N, Aoyagi M, Fujii S, Goto K.
    • Journal Title

      Histochem CellBiol

      Volume: 137 Issue: 4 Pages: 499-511

    • DOI

      10.1007/s00418-011-0907-y

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of inositol 1,4,5-trisphosphate receptors in the post synaptic expression of guinea pig hippocampal mossy fiber depotentiation2011

    • Author(s)
      Yamazaki Y
    • Journal Title

      Brain Res

      Volume: 1387 Pages: 19-28

    • DOI

      10.1016/j.brainres.2011.02.088

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired hippocampal long-term potentiation and failure of learning in β1,4-N-acetylgalactosaminyl transferase gene transgenic mice2011

    • Author(s)
      Ikarashi K, Fujiwara H, Yamazaki^* Y, Goto JI, Kaneko K, Kato H, Fujii S, Sasaki H, Fukumoto S, Furukawa K, Waki H, Furukawa K.
    • Journal Title

      corresponding^* author

      Volume: 21 Issue: 10 Pages: 1373-1381

    • DOI

      10.1093/glycob/cwr090

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 電気的リモデリングに対するベプリジルの作用2010

    • Author(s)
      石井邦明
    • Journal Title

      心電図

      Volume: 30 Pages: 142-142

    • NAID

      10027704736

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Nicotine facilitates long-term potentiation induction in oriens-lacunosummolecular cells via Ca^<2+> entry through non-α7 nicotinic acetylcholine receptors2010

    • Author(s)
      Jia, Yamazaki, et al.
    • Journal Title

      European Journal of Neuroscience

      Volume: 31 Pages: 463-476

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular calcium ion dynamics involved in long-term potentiation in hippocampal CA1 neurons in mice lacking the IP3 type 1 receptor2010

    • Author(s)
      Yoshioka, Yamazaki, et al.
    • Journal Title

      Neuroscience Research

      Volume: 67 Pages: 149-155

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] α_<1A>および α_<1B>アドレナリン受容体刺激による KCNQ1のインターナリゼーション2013

    • Author(s)
      倉上和也
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡(福岡国際会議場)
    • Year and Date
      2013-03-22
    • Related Report
      2012 Final Research Report
  • [Presentation] α1Aおよびα1Bアドレナリン受容体刺激によるKCNQ1のインターナリゼーション2013

    • Author(s)
      倉上和也
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      福岡(福岡国際会議場)
    • Related Report
      2012 Annual Research Report
  • [Presentation] タンパク質型Ca2+インジケーターによる小胞体内腔Ca2+動態の可視化と機能解析2013

    • Author(s)
      鈴木純二
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      福岡(福岡国際会議場)
    • Related Report
      2012 Annual Research Report
  • [Presentation] アンジオテンシン受容体 1型および α_<1A>受容体刺激による KCNQ1のインターナリゼーション機構2012

    • Author(s)
      石井邦明
    • Organizer
      第22回日本循環薬理学会
    • Place of Presentation
      富山(富山国際会議場)
    • Year and Date
      2012-11-30
    • Related Report
      2012 Final Research Report
  • [Presentation] Gq蛋白共役型受容体による Q1/E1チャネルのエンドサイトーシス2012

    • Author(s)
      石井邦明
    • Organizer
      第29回日本心電学会学術集会
    • Place of Presentation
      千葉(幕張メッセ国際会議場)
    • Year and Date
      2012-10-13
    • Related Report
      2012 Final Research Report
  • [Presentation] Facilitative effects of oligodendrocytes depolarization on the axonal conduction in the white matter of murine hippocampus2012

    • Author(s)
      山崎良彦
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋市(名古屋国際会議場)
    • Year and Date
      2012-09-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Modulatory effects of periinterneuronal oligodendrocyte on interneuronal firing in CA1 region of rat hippocampus2012

    • Author(s)
      山崎良彦
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      松本市(長野県松本文化会館)
    • Year and Date
      2012-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] インスリンによる KCNQ1/ KCNE1電流の抑制には KCNE1が必須である2012

    • Author(s)
      呉明華
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都(国立京都国際会館)
    • Year and Date
      2012-03-15
    • Related Report
      2012 Final Research Report
  • [Presentation] インスリンによるKCNQ1/KCNE1電流の抑制にはKCNE1が必須である2012

    • Author(s)
      呉明華, 他
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      京都(国立京都国際会館)
    • Year and Date
      2012-03-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] タンパク質型Ca^<2+>インジケーターによる小胞体内腔Ca^<2+>動態の可視化と機能解析2012

    • Author(s)
      鈴木純二, 他
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      京都(国立京都国際会館)
    • Year and Date
      2012-03-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 軸索・シュワン細胞間ATPシグナルを介したミエリン鞘形成機構2012

    • Author(s)
      稲生大輔, 他
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      京都(国立京都国際会館)
    • Year and Date
      2012-03-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] インスリンによる KCNQ1/ KCNE1電流の修飾メカニズム2012

    • Author(s)
      呉 明華
    • Organizer
      第41回日本心脈管作動物質学会
    • Place of Presentation
      秋田(秋田キャッスルホテル)
    • Year and Date
      2012-02-10
    • Related Report
      2012 Final Research Report
  • [Presentation] インスリンによるKCNQ1/KCNE1電流の修飾メカニズム2012

    • Author(s)
      呉明華, 他
    • Organizer
      日本心脈管作動物質学会
    • Place of Presentation
      秋田(秋田キャッスルホテル)
    • Year and Date
      2012-02-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] インスリンおよびIGF-1によるIKs電流の修飾機構2012

    • Author(s)
      呉 明華
    • Organizer
      日本薬理学会北部会
    • Place of Presentation
      新潟(朱鷺メッセ)
    • Related Report
      2012 Annual Research Report
  • [Presentation] ERK5とERK1/2のクロストーク機構の解析2012

    • Author(s)
      小原祐太郎
    • Organizer
      日本薬理学会北部会
    • Place of Presentation
      新潟(朱鷺メッセ)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Gq蛋白共役型受容体によるQ1/E1チャネルのエンドサイトーシス2012

    • Author(s)
      石井邦明
    • Organizer
      日本心電学会学術集会
    • Place of Presentation
      千葉(幕張メッセ)
    • Related Report
      2012 Annual Research Report
  • [Presentation] アンジオテンシン受容体1型およびα1A受容体刺激によるKCNQ1のインターナリゼーション機構2012

    • Author(s)
      岡崎 雅
    • Organizer
      日本循環薬理学会
    • Place of Presentation
      富山(富山国際会議場)
    • Related Report
      2012 Annual Research Report
  • [Presentation] インスリンによるKCNQ1/KCNE1電流の抑制と増大2011

    • Author(s)
      石井邦明, 他
    • Organizer
      日本循環薬理学会
    • Place of Presentation
      岡山(岡山大学50周年記念館)
    • Year and Date
      2011-12-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] インスリンによる I_<Ks>電流の修飾における KCNE1の関与2011

    • Author(s)
      呉 明華
    • Organizer
      第62回日本薬理学会北部会
    • Place of Presentation
      仙台(江陽グランドホテル)
    • Year and Date
      2011-09-29
    • Related Report
      2012 Final Research Report
  • [Presentation] インスリンによるIKs電流の修飾におけるKCNE1の関与2011

    • Author(s)
      呉明華, 他
    • Organizer
      日本薬理学会北部会
    • Place of Presentation
      仙台(江陽グランドホテル)
    • Year and Date
      2011-09-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Augmentation of KCNQ1/KCNE1 currents by insulin treatment2011

    • Author(s)
      呉明華, 他
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] シュワン細胞におけるATP-イノシトール1, 4, 5三リン酸シグナルを介したミエリン鞘形成機構2011

    • Author(s)
      稲生大輔, 他
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] タンパク質型Ca^<2+>インジケーターによる小胞体内腔Ca^<2+>動態の可視化と機能解析2011

    • Author(s)
      鈴木純二, 他
    • Organizer
      日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] I_<Ks>チャネルの修飾機構 :質的修飾と量的修飾2010

    • Author(s)
      石井邦明
    • Organizer
      第27回日本心電学会学術集会
    • Place of Presentation
      大分(iichiko総合文化センター)
    • Year and Date
      2010-10-09
    • Related Report
      2012 Final Research Report
  • [Presentation] Ix_8チャネルの修飾機構:質的修飾と量的修飾2010

    • Author(s)
      石井邦明
    • Organizer
      日本心電学会学術集会
    • Place of Presentation
      大分
    • Year and Date
      2010-10-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effects of insulin on KCNQ1/ KCNE1 channel expressed in Xenopus oocytes2010

    • Author(s)
      呉 明華
    • Organizer
      第61回日本薬理学会北部会
    • Place of Presentation
      札幌(札幌コンベンションセンター)
    • Year and Date
      2010-09-10
    • Related Report
      2012 Final Research Report
  • [Presentation] α_<1A>アドレナリン受容体刺激によるインターナリゼーション KCNQ1インターナリゼーションのメカニズム2010

    • Author(s)
      蔦川修生
    • Organizer
      第61回日本薬理学会北部会
    • Place of Presentation
      札幌(札幌コンベンションセンター)
    • Year and Date
      2010-09-10
    • Related Report
      2012 Final Research Report
  • [Presentation] α1Aアドレナリン受容体刺激によるKCNQ1インターナリゼーションのメカニズム2010

    • Author(s)
      蔦川修生, 他
    • Organizer
      日本薬理学会北部会
    • Place of Presentation
      札幌
    • Year and Date
      2010-09-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effects of insulin on KCNQ1/KCNE1 channel expressed in Xenopus oocytes2010

    • Author(s)
      呉明華, 他
    • Organizer
      日本薬理学会北部会
    • Place of Presentation
      札幌
    • Year and Date
      2010-09-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Internalization of KCNQ1 protein by activation of AT1 receptor and α_1 adrenergic receptor2010

    • Author(s)
      Tsutakawa Shusei
    • Organizer
      XX World Congress ISHR
    • Place of Presentation
      Kyoto (Kyoto International Conference Center)
    • Year and Date
      2010-05-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Internalization of KCNQ1 protein by activation of AT, receptor and α_1 adrenergic receptor2010

    • Author(s)
      Tsutakawa S, et al.
    • Organizer
      World Congress of the ISHR
    • Place of Presentation
      京都
    • Year and Date
      2010-05-16
    • Related Report
      2010 Annual Research Report
  • [Book] 薬理学(インテグレーテッドシリーズ4)2010

    • Author(s)
      中畑則道, 他
    • Publisher
      東京化学同人
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.id.yamagata-u.ac.jp/Pharmaco/pharmacology/Top.html

    • Related Report
      2012 Final Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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