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Proton leak mechanisms in acidic environments

Research Project

Project/Area Number 15K08184
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Kuno Miyuki  大阪市立大学, 大学院医学研究科, 准教授 (00145773)

Co-Investigator(Kenkyū-buntansha) 酒井 啓  大阪市立大学, 大学院医学研究科, 研究員(移行) (90382192)
Co-Investigator(Renkei-kenkyūsha) NOTOMI Takuya  大阪歯科大学, 歯学研究科, 講師 (70542249)
Research Collaborator LI Gunagshuai  , 大学院学生
KAIJU Taro  , 学部学生
MORIURA Yoshie  , 研究補佐
HINO Yoshiko  , 研究補佐
KAWAWAKI Junko  , 技術職員
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: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords生体膜 / チャネル / トランスポータ / 能動輸送 / プロトン
Outline of Final Research Achievements

There are many local acidic spots in both intracellular and extracellular spaces. The pH level, intimately related to each specific function, is maintained by balancing acidification by proton (H+) pumps and its elimination (alkalization) by H+ leak mechanisms. The molecular entity and the property of the H+ leak remain to be clarified. We demonstrated the acid-inducible H+ leak in the plasma membrane of osteoclasts which resorb bone tissues by secreting massive amounts of acids on the bone surface. We also revealed that inorganic phosphates stimulated voltage-gated H+ channels and that the pH in single phagosomes often oscillates, which might contribute to H+ leakages in the specific occasions. These findings help us to clarify physiological/pathological mechanisms of regulation of acidic environments by H+ leak mechanisms.

Report

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

    (38 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 10 results,  Acknowledgement Compliant: 6 results) Presentation (21 results) (of which Int'l Joint Research: 6 results,  Invited: 8 results) Book (2 results) Remarks (3 results)

  • [Int'l Joint Research] University of Shefield(英国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Cooperative electrogenic proton transport pathways in the plasma membrane of the proton-secreting osteoclast (Invited Review)2018

    • Author(s)
      Kuno M
    • Journal Title

      Pflugers Archives - European Journal of Physiology

      Volume: 470 Issue: 6 Pages: 851-866

    • DOI

      10.1007/s00424-018-2137-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Letter to the Editor regarding Tsujikawa and lipid emulsion: In response2018

    • Author(s)
      Tsujikawa S, Matsuura T, Hori K, Mori T, Kuno M, Nishikawa K
    • Journal Title

      Anesthesia and Analgesia

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Journal Article] Superior efficacy of lipid emulsion infusion over serum alkalinization in reversing amitriptyline-induced cardiotoxicity in guinea pig2018

    • Author(s)
      Tsujikawa S, Matsuura T, Hori K, Mori T, Kuno M, Nishikawa K
    • Journal Title

      Anesthesia and Analgesia

      Volume: 126 Issue: 4 Pages: 1159-1169

    • DOI

      10.1213/ane.0000000000002707

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of lysosomal channel protein TPC2 in osteoclast differentiation and bone remodeling under normal and low-magnesium conditions.2017

    • Author(s)
      Notomi Takuya, Kuno M, Hiyama A, Nozaki T, Ohura K, Ezura Y, Noda M,
    • Journal Title

      J Biol Chem

      Volume: 292 Issue: 51 Pages: 20998-21010

    • DOI

      10.1074/jbc.m117.780072

    • NAID

      130007900094

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular phosphates enhance activities of voltage-gated proton channels and production of reactive oxygen species in murine osteoclast-like cells2017

    • Author(s)
      Li G, Miura K and Kuno M
    • Journal Title

      Pflügers Archiv - Eur J Physiol.

      Volume: 469 Issue: 2 Pages: 279-292

    • DOI

      10.1007/s00424-016-1931-5

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CRAC3 regulates the stability of non-excitable vesicle fusion pores in a Ca2+-independent manner via molecular interaction with syntaxin42016

    • Author(s)
      Liu S, Sahid MNA, Takemasa E, Kiyoi T, Kuno M, Oshima Y and Maeyama K
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 1-14

    • DOI

      10.1038/srep28133

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells2016

    • Author(s)
      Kuno M, Li G, Moriura Y, Hino Y, Kawawaki J and Sakai H
    • Journal Title

      Pflugers Archiv (Eur. J. Physiol.)

      Volume: 468 Issue: 5 Pages: 837-847

    • DOI

      10.1007/s00424-016-1796-7

    • NAID

      120006359120

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2020356

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 電位依存性プロトンチャネル2016

    • Author(s)
      久野みゆき
    • Journal Title

      腎と透析

      Volume: 80 Pages: 397-401

    • Related Report
      2015 Research-status Report
  • [Journal Article] The significant contribution of the partitioning effect in lipid resuscitation for bupivacaine-induced cardiotoxicity: Evaluation by using centrifuged solution in vivo and in isolated hearts2015

    • Author(s)
      Hori,K, Matsuura T, Tsujikawa S, Mori T, Kuno M and Nishikawa K
    • Journal Title

      Br J Anaesth

      Volume: 115 Issue: 6 Pages: 935-937

    • DOI

      10.1093/bja/aev386

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Membrane depolarization regulates intracellular RANKL transport in non-excitable osteoblasts2015

    • Author(s)
      Notomi T, Kuno M, Ezura Y, Honma M, Ishizuka T, Ohura K, Yao H and Noda M.
    • Journal Title

      Bone

      Volume: 81 Pages: 306-314

    • DOI

      10.1016/j.bone.2015.07.031

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Zinc-induced effects on osteoclastogenesis involve activation of hyperpolarization-activated cyclic nucleotide modulated channels via changes in membrane potential2015

    • Author(s)
      Notomi T, Kuno M, Ohura K, Noda M and Skerry TM
    • Journal Title

      J Bone Miner Res

      Volume: 30 Issue: 9 Pages: 1618-1626

    • DOI

      10.1002/jbmr.2507

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Rapid oscillations of phagosomal pH in RAW264-derived osteoclasts2018

    • Author(s)
      Kuno M, Kaiju T, Moriura Y, Hino Y, Kawawaki J, Sakai H
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Extracellular phosphate is an endogenous regulator for voltage-gated proton channels and production of reactive oxygen species in osteoclasts2018

    • Author(s)
      Li G, Miura K, Hino Y, Moriura Y, Kawawaki J, Sakai H, Kuno M
    • Organizer
      62th Annual Meeting of Biophysical Society (米国生物物理学会)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞外リン酸は破骨細胞のプロトンチャネル活性と活性酸素産生を調節する共通シグナルである2017

    • Author(s)
      李光帥、日野佳子、森浦芳枝、川脇順子、酒井啓、三浦克之、久野みゆき
    • Organizer
      第94回生理学会大会
    • Place of Presentation
      浜松アクトシティコングレスセンター(静岡県浜松市)
    • Year and Date
      2017-03-29
    • Related Report
      2016 Research-status Report
  • [Presentation] RAW264およびRAW264由来破骨細胞におけるphagosomal pH のオシレーション2017

    • Author(s)
      久野みゆき、海住太郎、森浦芳枝、日野佳子、川脇順子、酒井啓
    • Organizer
      平成29年度生理研研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Role of the lysosomal channel, Two Pore Channel 2, in osteoclast differentiation and bone remodeling under normal and low-magnesium conditions2017

    • Author(s)
      Notomi T, Kuno M., Hiyama A, Ezura Y, Ohura K, Noda M
    • Organizer
      39th ASBMR (米国骨代謝学会)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Extracellular phosphate-sensing regulation of voltage-gated proton channels and reactive oxygen species in osteoclasts2017

    • Author(s)
      Li G, Miura K, Hino Y, Moriura Y, Kawawaki J, Sakai H, Kuno M
    • Organizer
      2nd Ion channel modulation symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 破骨細胞のH+チャネルを介する細胞外リン酸濃度の感受・応答メカニズム2016

    • Author(s)
      久野みゆき、李光帥、三浦克之、日野佳子、森浦芳枝、川脇順子、酒井啓
    • Organizer
      平成28年度生理研研究会
    • Place of Presentation
      生理学研究所(愛知県岡崎市)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] RAW細胞由来破骨細胞におけるリン酸による電位依存性H+チャネル活性の増強2016

    • Author(s)
      李光帥、三浦克之、久野みゆき
    • Organizer
      第109回近畿生理学談話会
    • Place of Presentation
      大阪市立大学医学部(大阪府大阪市)
    • Year and Date
      2016-11-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Superiority of lipid Infusion over serum alkalinization in reversal of amitriptyline cardiotoxicity in guinea pigs2016

    • Author(s)
      Tsujikawa S, Matsuura T, Hori K, Mori T, Kuno M, and Nishikawa K
    • Organizer
      2016 米国麻酔科学会年会
    • Place of Presentation
      マコーミックプレイス(米国、シカゴ)
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Changes in membrane potential regulates RANKL intracellular transport via voltage-gated calcium channels in osteoblasts2016

    • Author(s)
      Notomi T, Kuno M, Hiyama A, Ezura Y, Ohura K and Noda M
    • Organizer
      2016米国骨代謝学会(ASBMR)
    • Place of Presentation
      ジョージアワールドコングレスセンター (米国、アトランタ)
    • Year and Date
      2016-09-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 破骨細胞における電位依存性H+チャネルの内因性調節機構:無機リン酸の役割2016

    • Author(s)
      久野みゆき、李光帥、三浦克之、日野佳子、森浦芳枝、川脇順子、酒井啓
    • Organizer
      平成28年度生理研研究会
    • Place of Presentation
      生理学研究所(愛知県岡崎市)
    • Year and Date
      2016-09-15
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 破骨細胞のH+ flux機構2016

    • Author(s)
      久野みゆき、酒井啓、李光帥、日野佳子、森浦芳枝、川脇順子
    • Organizer
      平成28年度生理研研究会
    • Place of Presentation
      生理学研究所(愛知県岡崎市)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] RAW細胞由来破骨細胞における電位依存性H+チャネルの調節機構:無機リン酸によるH+排出の増強2016

    • Author(s)
      李光帥、久野みゆき
    • Organizer
      第34回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] RAW264由来破骨細胞膜における新規の酸感受性プロトン流入機構2016

    • Author(s)
      久野みゆき、李光帥、酒井啓
    • Organizer
      第34回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] アミトリプチリン中毒に対する脂肪乳剤の有効性―アルカリ化療法との比較―(優秀演題)2016

    • Author(s)
      辻川翔吾, 松浦正, 堀耕太郎, 森隆, 久野みゆき, 西川精宣
    • Organizer
      日本麻酔科学会第63回学術集会
    • Place of Presentation
      福岡国際会議場 (福岡県福岡市)
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report
  • [Presentation] H+選択的膜輸送体の機能:プロトンポンプとプロトンチャネル2016

    • Author(s)
      久野みゆき
    • 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
      2016-03-24
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] マウス破骨細胞において細胞外リン酸はType II Na-Pi transporterを介して電位依存性H+チャネル活性を増強するType II Na-Pi transporters mediate extracellular phosphate-induced potentiation of the voltage-gated H+ channels in murine osteoclast-like cells.2016

    • Author(s)
      李光師、三浦克之、久野みゆき
    • 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
      2016-03-23
    • Related Report
      2015 Research-status Report
  • [Presentation] Behaviors of the voltage-gated H+ channels under pH disturbances in osteoclasts(pH環境の変化に対する破骨細胞H+チャネルの応答様式)2016

    • Author(s)
      Miyuki Kuno
    • 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] Zinc-induced effects on osteoclastogenesis involves activation of HCN channels via changes in membrane potential2015

    • Author(s)
      Takuya Notomi, Miyuki Kuno, Akiko Hiyama, Kiyoshi Ohura, Masaki Noda and Timothy M. Skerry
    • Organizer
      第37回米国骨代謝学会
    • Place of Presentation
      シアトルコンベンションセンター(米国)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Real-time analysis of V-ATPase (proton pump) currents in the plasma membrane of osteoclasts (破骨細胞における細胞膜V-ATPase電流の経時的解析)2015

    • Author(s)
      久野みゆき
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 破骨細胞膜における酸感受性プロトンリーク機構の定量的検討2015

    • Author(s)
      久野みゆき、李光師、森浦芳枝、日野佳子、川脇順子、酒井啓
    • Organizer
      平成27年度生理学研究所研究会 「生体シグナルダイナミクス」
    • Place of Presentation
      生理学研究所(愛知県岡崎市)
    • Year and Date
      2015-09-03
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] 骨ペディア/ 骨疾患・骨代謝キーワード事典2015

    • Author(s)
      久野みゆき
    • Total Pages
      327
    • Publisher
      羊土社
    • Related Report
      2015 Research-status Report
  • [Book] 生理学問題集(CBT準拠)2015

    • Author(s)
      久野みゆき
    • Total Pages
      179
    • Publisher
      文光堂
    • Related Report
      2015 Research-status Report
  • [Remarks] 分子細胞生理学

    • Related Report
      2017 Annual Research Report
  • [Remarks] 分子細胞生理学

    • Related Report
      2016 Research-status Report
  • [Remarks] 分子細胞生理学

    • URL

      http://www.med.osaka-cu.ac.jp/molcelphysiol/

    • Related Report
      2015 Research-status Report

URL: 

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

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