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Elucidation of molecular entities responsible for unique electrochemical property of the cochlear lateral wall

Research Project

Project/Area Number 17K17736
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
General pharmacology
Research InstitutionNiigata University

Principal Investigator

Sawamura Seishiro  新潟大学, 医歯学系, 助教 (10781974)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords内耳蝸牛 / イオン輸送 / トランスポーター / 質量分析 / チャネル
Outline of Final Research Achievements

The cochlea in the inner ear is filled with a unique extracellular solution that exhibits a highly positive potential of +80 mV. This property is essential for hearing and likely to be maintained by ion transport across cochlear lateral wall made up of two epithelial layers. In our earlier work, we found that the outer layer of the lateral wall has Na+ permeability which contributes to highly positive endocochlear potential. Nevertheless, its molecular entity remained elusive. In this study, we identified 5 channels and 19 transporters expressed in the outer layer by proteomic analysis. In addition, by in vitro and in vivo electrophysiological experiments, we found that one of the transporters showed Na+ permeability and perfusion of its inhibitor to the cochlea decreased endocochlear potential. These results suggest that the identified transporter has essential role in the Na+ permeability of the lateral wall and maintenance of electrochemical property of the cochlea.

Academic Significance and Societal Importance of the Research Achievements

内耳性障害性難聴に対する効果的な治療法は未だほとんどない。この課題を解決するためには、内耳蝸牛の聴覚機能に関する理解を深めることが重要である。本研究では、これまであまり調べられてこなかった蝸牛側壁外層に発現するタンパク質を網羅的に解析し、聴覚に必須な内耳電位の維持に関わる新たなイオン輸送体を同定した。この成果は、聴覚生理の基礎的知見を広げるだけでなく、難聴の病因解明や治療法の開発に役立つことが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 2 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Characterisation of the static offset in the travelling wave in the cochlear basal turn2020

    • Author(s)
      T. Ota, F. Nin, S. Choi, S. Muramatsu, S. Sawamura, G. Ogata, M. P. Sato, Kat. Doi, K. Doi, T. Tsuji, S. Kawano, T. Reichenbach, and H. Hibino
    • Journal Title

      Pflugers Archiv - European Journal of Physiology

      Volume: 472 Issue: 5 Pages: 1-11

    • DOI

      10.1007/s00424-020-02373-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterisation of N-glycans in the epithelial-like tissue of the rat cochlea2019

    • Author(s)
      Nonomura Yoriko、Sawamura Seishiro、Hanzawa Ken、Nishikaze Takashi、Sekiya Sadanori、Higuchi Taiga、Nin Fumiaki、Uetsuka Satoru、Inohara Hidenori、Okuda Shujiro、Miyoshi Eiji、Horii Arata、Takahashi Sugata、Natsuka Shunji、Hibino Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-21

    • DOI

      10.1038/s41598-018-38079-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fibrocytes in the cochlea of the mammalian inner ear: their molecular architecture, physiological properties, and pathological relevance2017

    • Author(s)
      Takamasa Yoshida, Seishiro Sawamura, Takeru Ota, Taiga Higuchi, Genki Ogata, Karin Hori, Nakagawa Takashi, Katsumi Doi, Mitsuo P Sato, Yoriko Nonomura, Arata Horii, Sugata Takahashi, Shizuo Komune, Fumiaki Nin, Hiroshi Hibino
    • Journal Title

      Medical Research Archives

      Volume: 5 Pages: 1-16

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Computer modeling defines the system driving a constant current crucial for homeostasis in the mammalian cochlea by integrating unique ion transports2017

    • Author(s)
      Nin F, et al.
    • Journal Title

      npj Systems Biology and Applications

      Volume: 3 Issue: 1 Pages: 4-4

    • DOI

      10.1038/s41540-017-0025-0

    • NAID

      130007901272

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A microsensing system for the in vivo real-time detection of local drug kinetics2017

    • Author(s)
      Ogata G, et al.
    • Journal Title

      Nature Biomedical Engineering

      Volume: 1 Issue: 8 Pages: 654-666

    • DOI

      10.1038/s41551-017-0118-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ダイヤモンドセンサを用いた複数薬物のリアルタイム同時定量2020

    • Author(s)
      澤村 晴志朗、緒方 元気、桑原 沙耶香、加藤 理都、浅井 開、ラズビナ オリガ、栄長 泰明、日比野 浩
    • Organizer
      第93回日本薬理学年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 針状ダイヤモンド電極による局所薬物動態の生体内実時間マイクロセンシングシステム2019

    • Author(s)
      緒方 元気、浅井 開、澤村 晴志朗、楠原 洋之、栄長 泰明、日比野 浩
    • Organizer
      NEURO2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] ダイヤモンドセンサを用いた複数薬物のリアルタイム定量2019

    • Author(s)
      澤村 晴志朗、緒方 元気、浅井 開、渡邉 航太、ラズビナ オリガ、栄長 泰明、日比野 浩
    • Organizer
      第70回日本薬理学会北部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ダイヤモンドセンサを用いた複数薬物のリアルタイム定量システム2019

    • Author(s)
      澤村 晴志朗、緒方 元気、浅井 開、桑原 沙耶香、加藤 理都、ラズビナ オリガ、栄長 泰明、日比野 浩
    • Organizer
      第66回中部日本生理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ダイヤモンドセンサによる血漿中の分子標的薬イマチニブの迅速測定2019

    • Author(s)
      澤村 晴志朗、ラズビナ オリガ、緒方 元気、渡邉 航太、浅井 開、花輪 藍、栄長 泰明、日比野 浩
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Proteomic analysis of the transport system in a connective tissue of the mammalian cochlea2019

    • Author(s)
      Seishiro Sawamura, Yoriko Nonomura, Fumiaki Nin, Arata Horii, Sugata Takahashi, Shushi Nagamori, Yoshikatsu Kanai, Hiroshi Hibino
    • Organizer
      9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comprehensive protein analysis of the transport system in a connective tissue of the inner ear.2018

    • Author(s)
      Seishiro Sawamura, Yoriko Nonomura, Fumiaki Nin, Satoru Uetsuka, Hidenori Inohara, Arata Horii, Sugata Takahashi, Shushi Nagamori, Yoshikatsu Kanai, Hiroshi Hibino
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 内耳蝸牛内リンパ液の恒常性に関与する らせん靭帯膜タンパク質の網羅的解析2017

    • Author(s)
      澤村晴志朗、野々村頼子、任書晃、上塚学、猪原秀典、 堀井新、髙橋姿、永森收志、金井好克、日比野浩
    • Organizer
      第68回北部薬理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 内耳蝸牛の特殊体液の恒常性維持に関与する 膜タンパク質の網羅的解析2017

    • Author(s)
      澤村晴志朗、野々村頼子、任書晃、上塚学、猪原秀典、 堀井新、髙橋姿、永森收志、金井好克、日比野浩
    • Organizer
      第64回中部生理学会
    • Related Report
      2017 Research-status Report
  • [Book] 生き物と音の事典 2-13 内耳の形と働き(ヒト)2019

    • Author(s)
      澤村 晴志朗、日比野 浩
    • Total Pages
      464
    • Publisher
      朝倉書店
    • ISBN
      9784254171679
    • Related Report
      2019 Annual Research Report
  • [Book] Clinical Neuroscience 神経系のトランスポーターupdate -トランスポーターの基礎「カリウム」-2018

    • Author(s)
      澤村 晴志朗、任 書晃、日比野 浩
    • Total Pages
      5
    • Publisher
      中外医学社
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 難聴の予防および/または治療用医薬組成物2019

    • Inventor(s)
      永田 龍、日比野 浩、森 泰生、澤村 晴志朗、任 書晃
    • Industrial Property Rights Holder
      永田 龍、日比野 浩、森 泰生、澤村 晴志朗、任 書晃
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-193880
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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