• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Conformation of Cav1.2 channel in the inactivated state by calmodulin binding

Research Project

Project/Area Number 16K08499
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

Minobe Etsuko  鹿児島大学, 医歯学域医学系, 講師 (00448581)

Research Collaborator Mori Masayuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsカルシウムチャネル / カルモジュリン / パッチクランプ法 / inside-out / Cav1.2 / カルシウムイオン / run-down / ATP / カルシムチャネル / カルシウム
Outline of Final Research Achievements

Activity of Cav1.2 channels requires calmodulin (CaM). Conformation of the channel-CaM complex has been reported, but they are still in debate. We have investigated the conformation of Cav1.2 channel in the inactivated state by recording the activity of carboxyl-terminal (CT) deletion channel linked to CaM (CaM-linked channel), W82A-CaM-linked channel and amino-terminal (NT) deletion CaM-linked channel (delN-CaM-linked channel), using the patch-clamp technique. The CaM-linked channel showed both Ca2+ and CaM dependent inactivation, while the W82A-CaM-linked channel and the delN-CaM-linked channel showed only CaM-dependent inactivation but not Ca2+-dependent inactivation. These results suggest that the inactivation induced by one CaM linked with channel may require the NT of the channel, while more than one CaM induced inactivation may take place without NT, but within CT of the channel. Thus, there might be two types of conformation of Ca2+-dependent inactivation of Cav1.2.

Academic Significance and Societal Importance of the Research Achievements

Cav1.2チャネルを含むL型Ca2+チャネルは、心筋、骨格筋、神経系や分泌細胞に分布し、筋収縮、遺伝子発現、シナプス伝達、ホルモン分泌などにおいて重要な役割をもつため、本研究により得られた知見を広く応用できる。また、カルモジュリンの遺伝子異常から病態につながる例も報告されており、カルモジュリンによるチャネルの活性調節は重要な位置づけにある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 2 results) Remarks (4 results)

  • [Journal Article] Purification of insoluble GST-fused and GST-cleaved Cav1.2 channel fragment by denaturation and renaturation.2019

    • Author(s)
      Qinghua Gao, Etsuko Minobe, Masaki Kameyama, Jianjun Xu
    • Journal Title

      Protein Expression and Purification

      Volume: 160 Pages: 7-10

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PKA phosphorylation of Cav1.2 channel modulates the interaction of calmodulin with the C terminal tail of the channel.2018

    • Author(s)
      Ming Lei, Jianjun Xu, Qinghua Gao, Etsuko Minobe, Masaki Kameyama, Liying Hao
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 137 Issue: 2 Pages: 187-194

    • DOI

      10.1016/j.jphs.2018.05.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The effect of Ca2+, lobe-specificity, and CaMKII on CaM binding to NaV1.1.2018

    • Author(s)
      Jianing Li, Zhiyi Yu, Jianjun Xu, Rui Feng, Qinghua Gao, Tomasz Boczek, Junyan Liu, Zhi Li, Qianhui Wang, Ming Lei, Jian Gong, Huiyuan Hu, Etsuko Minobe, Hong-Long Ji, Masaki Kameyama, Feng Guo
    • Journal Title

      Intetnational Journal of Molecular Science

      Volume: 19 Issue: 9 Pages: 2495-2510

    • DOI

      10.3390/ijms19092495

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A new interaction between proximal and distal C-terminus of Cav1.2 channels2017

    • Author(s)
      Lyu Liting、Gao Qinghua、Xu Jianjun、Minobe Etsuko、Zhu Tong、Kameyama Masaki
    • Journal Title

      Journal of pharmacological sciences

      Volume: 133 Issue: 4 Pages: 240-246

    • DOI

      10.1016/j.jphs.2017.03.002

    • Related Report
      2017 Research-status 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
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of protein phosphatases in the run down of guinea pig cardiac Cav1.2 Ca2+ channels.2016

    • Author(s)
      Lifeng Yu, Jianjun Xu, Etsuko Minobe, Asako Kameyama, Lei Yang, Rui Feng, Liying Hao, Masaki Kameyama.
    • Journal Title

      American Journal of Physiology. Cell Physiolgy.

      Volume: 310 Issue: 10 Pages: C773-C779

    • DOI

      10.1152/ajpcell.00199.2015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] tructure analysis of the binding between Cav1.2 channel and calmodulin.2019

    • Author(s)
      Masaki Kameyama, Etsuko Minobe, Jianjun Xu, Qinghua Gao
    • Organizer
      9th FAOPS Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cav1.2 channel inactivation induced by two molecules of calmodulin.2019

    • Author(s)
      Etsuko Minobe, Masayuki X Mori, Masaki Kameyama
    • Organizer
      9th FAOPS Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cav1.2型Caチャネルへのカルモジュリンの結合モデル:分子シミュレーション研究2018

    • Author(s)
      亀山正樹、蓑部悦子、徐建軍、高青華
    • Organizer
      第69回西日本生理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] カルモジュリンのCav1.2型Caチャネルへの結合の分子シミュレーション2018

    • Author(s)
      亀山正樹、蓑部悦子、徐建軍、高青華
    • Organizer
      生理学研究所研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cav1.2 channel regulation by calmodulin and ATP: A study on genetically mutated channels.2018

    • Author(s)
      Etsuko Minobe, Masayuki X Mori, Masaki Kameyama.
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cav1.2 channel regulation by PKA phosphorylation involves modulation of calmodulin binding to the channels.2018

    • Author(s)
      Qingha Gao, Ming Lei, Jianjun Xu, Etsuko Minobe, Yaonan Zhu, Liying Hao, Masaki Kameyama.
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status 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2018

    • Author(s)
      高 青華、雷 明、徐 建軍、蓑部 悦子、朱 曜南、Hao 麗英、亀山 正樹
    • Organizer
      第68回西日本生理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Regulation of Cav1.2 channels by calmodulin: A study on genetically mutated channels.2017

    • Author(s)
      Etsuko Minobe, Masayuki X Mori, Masaki Kameyama
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松 (静岡県・浜松市中区板屋町)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] The mechanism for PKA-mediated facilitation of Cav1.2 channel: a new model2017

    • Author(s)
      Liting Lyu, Qinghua Gao, Ming Lei, Jianjun Xu, Etsuok Minobe, Masaki Kameyama
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松 (静岡県・浜松市中区板屋町)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Cav1.2型Ca2+チャネルC末端部のチャネル活性調節機序2016

    • Author(s)
      高 青華、徐 建軍、Lyu Liting、蓑部 悦子、Hao Liying、亀山 正樹
    • Organizer
      生理学研究所研究会
    • Place of Presentation
      九州大学馬出キャンパス (福岡県・福岡市東区馬出)
    • Year and Date
      2016-10-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Cav1.2型Ca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、Lyu Liting、蓑部 悦子、Hao Liying、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・鹿児島市桜島横山町)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Remarks] 鹿児島大学大学院医歯学総合研究科研究室紹介

    • URL

      https://www2.kufm.kagoshima-u.ac.jp/field/advanced-therapeutics/f101/02.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 鹿児島大学大学院医歯学総合研究科神経金生理学教室ホームページ

    • URL

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

    • Related Report
      2018 Annual Research Report
  • [Remarks] 鹿児島大学大学院医歯学総合研究科研究室紹介

    • URL

      http://www2.kufm.kagoshima-u.ac.jp/field/advanced-therapeutics/f101/02.html

    • Related Report
      2017 Research-status Report 2016 Research-status Report
  • [Remarks] 鹿児島大学大学院医歯学総合研究科神経筋生理学教室ホームページ

    • URL

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

    • Related Report
      2017 Research-status Report 2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi