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Study on the regulatory mechanisms of L-type Ca2+ channels

Research Project

Project/Area Number 15K08181
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionKagoshima University

Principal Investigator

KAMEYAMA Masaki  鹿児島大学, 医歯学総合研究科, 客員研究員 (60150059)

Co-Investigator(Kenkyū-buntansha) 徐 建軍  鹿児島大学, 医歯学域医学系, 講師 (10581689)
Co-Investigator(Renkei-kenkyūsha) MINOBE Etsuko  鹿児島大学, 医歯学域医学系, 講師 (00448581)
GAO Qinghua  鹿児島大学, 医歯学総合研究科, 特任研究員 (60813524)
Research Collaborator MORI Tomoyuki  京都大学, 工学研究科, 准教授
HAO Liying  中国医科大学, 薬学院薬理毒理学, 教授
ZHU Tong  東北大学, 機械工程及自動化学院, 教授
LYU Liting  東北大学, 機械工程及自動化学院, 大学院生
LEI Ming  中国医科大学, 薬学院薬理毒理学, 大学院生
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsCaチャネル / Aキナーゼ / カルモジュリン / 心筋 / Ca2+依存性調節 / リン酸化 / Ca2+ チャネル / 心筋細胞 / イオンチャネル
Outline of Final Research Achievements

We have investigated mechanisms underlying Cav1.2 Ca2+ channel regulation. We have found that: 1) the Ca2+ channels bind with protein kinase A (PKA) and protein phosphatases even in the inside-out mode; 2) there is a new interaction between CaM-binding region in the proximal C-terminal (CT1) and a region in the distal C-terminal (CT3) of alpha1C subunit; 3) PKA phosphorylation of CT1 affects the binding not only between CaM and CT1 but also the new proximal-distal (CT1-CT3) interaction. These results suggest that PKA phosphorylation regulate the Cav1.2 channel activity, at least partially, via affecting the CaM-CT1 interaction.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (11 results) (of which Invited: 2 results) Remarks (2 results)

  • [Int'l Joint Research] 中国医科大学(中国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] 中国医科大学/東北大学(中国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] 中国医科大学(中国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] A novel role of the antitumor agent tricyclodecan-9-yl-xanthogenate as an open channel blocker of KCNQ1/KCNE12018

    • Author(s)
      Wu, MK, Takemoto M, Luo H, Xu JJ, Lu MH, Kameyama M, Takumi T, Song WJ
    • Journal Title

      Eur J Pharmacol

      Volume: 824 Pages: 99-107

    • DOI

      10.1016/j.ejphar.2018.02.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Calmodulin and ATP support activity of the Cav1.2 channel through dynamic interactions with the channel.2017

    • Author(s)
      Minobe E, Mori MX, Kameyama M.
    • Journal Title

      J Physiol.

      Volume: 595 Issue: 8 Pages: 2465-2477

    • DOI

      10.1113/jp273736

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new interaction between proximal and distal C-terminus of Cav1.2 channels.2017

    • Author(s)
      Lyu L, Gao Q, Xu JJ, Minobe E, Zhu T, Kameyama M
    • Journal Title

      J Pharmacol Sci

      Volume: 133 Pages: 240-246

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] PKA and phosphatases attached to the Cav1.2 channel regulate channel activity in cell-free patches.2016

    • Author(s)
      Xu JJ, Yu LF, Minobe E, Lu LT, Lei M, Kameyama M
    • Journal Title

      Am J Physiol

      Volume: 310 Issue: 2 Pages: C136-C141

    • DOI

      10.1152/ajpcell.00157.2015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Nucleotides maintain the activity of Cav1.2 channels in guinea-pig ventricular myocytes.2015

    • Author(s)
      Liu SY, Xu JJ, Minobe E, Gao QH, Feng R, Zhao MM, Guo F, Yang L, Kameyama M, Hao LY
    • Journal Title

      Biophys Biochem Res Comm

      Volume: 460 Issue: 3 Pages: 813-818

    • DOI

      10.1016/j.bbrc.2015.03.111

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel.2015

    • Author(s)
      Sun Y, Xu JJ, Minobe E, Shimoara S, Hao LY, Kameyama M
    • Journal Title

      J Pharmacol Sci

      Volume: 128 Issue: 3 Pages: 137-143

    • DOI

      10.1016/j.jphs.2015.06.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mg2+-dependent facilitation and inactivation of L-type Ca2+ channel in guinea pig ventricular myocytes.2015

    • Author(s)
      Zhao MM, Feng R, Shao DX, Liu SY, Lei M, Wang HM, Sun XF, Guo F, Hu HY, Kameyama M, Hao LY
    • Journal Title

      J Pharmacol Sci

      Volume: 129 Issue: 3 Pages: 143-149

    • DOI

      10.1016/j.jphs.2015.08.001

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] カルモジュリンとATPによるCav1.2チャネルの制御機構2018

    • Author(s)
      蓑部悦子、森誠之、亀山正樹
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cav1.2型チャネルC末端の自己調節を基にしたPKAリン酸化のチャネル調節機序2018

    • Author(s)
      高青華、雷明、徐建軍、蓑部悦子、朱曜南、ハオ麗英、亀山正樹
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経細胞とCa2+チャネル2017

    • Author(s)
      亀山正樹
    • Organizer
      鹿児島神経科学研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Regulation of Cav1.2 channels by calmodulin: A study on genetically mutated channels2017

    • Author(s)
      蓑部悦子、森誠之、亀山正樹
    • Organizer
      第94回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The mechanism for PKA-mediated facilitation of Cav1.2 channel: A new model2017

    • Author(s)
      呂力ティン, 高青華, 雷明, 徐建軍, 蓑部悦子, 亀山正樹.
    • Organizer
      第94回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cav1.2 型Ca2+チャネルC 末端部におけるPKAリン酸化のチャネル活性調節機序2017

    • Author(s)
      高青華、雷明、徐建軍、蓑部悦子、朱曜南、ハオ麗英、亀山正樹
    • Organizer
      第68回西日本生理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cav1.2型Ca2+チャネルC末端部のチャネル活性調節作用2016

    • Author(s)
      高青華、徐建軍、呂力Ting、蓑部悦子、Hao麗英、亀山正樹
    • Organizer
      第67回西日本生理学会
    • Place of Presentation
      レインボー桜島(鹿児島県鹿児島市)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 2サイトモデルによるCav1.2チャネル調節の検討.2016

    • Author(s)
      河路広大、蓑部悦子、森誠之、亀山正樹
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Cav1.2 channelの活性を調節する細胞内因子2016

    • Author(s)
      亀山正樹
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Mechanism underlying PKA-mediated facilitation of cardiac Cav1.2 channels.2015

    • Author(s)
      呂力Ting、雷 明、徐建軍、蓑部悦子、矢沢和人、亀山正樹
    • Organizer
      第66回西日本生理学会
    • Place of Presentation
      久留米大学(福岡県久留米市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Cav1.2型チャネルC末端部切断変異体に対するカルモジュリンとATPの作用.2015

    • Author(s)
      蓑部悦子、森誠之、亀山正樹
    • Organizer
      第66回西日本生理学会
    • Place of Presentation
      久留米大学(福岡県久留米市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Remarks] http://www.kufm.kagoshima-u.ac.jp/~physiol2/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 鹿児島大学大学院医歯学総合研究科神経筋生理学研究室

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~physiol2/

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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