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P2X receptors contribute visual information processing in the mouse retina

Research Project

Project/Area Number 19K09939
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionNippon Medical School

Principal Investigator

Ishii Toshiyuki  日本医科大学, 医学部, 准教授 (10643140)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsP2X受容体 / ATP / 網膜 / 網膜神経節細胞 / アマクリン細胞 / 視覚 / P2X3受容体
Outline of Research at the Start

P2X受容体はATPの受容体として、近年、痛みや味覚の受容、脳におけるシナプス伝達機構などに重要な役割を果たしていることが明らかになってきた。P2X受容体は網膜においても広く発現が認められることから、視覚においてもP2X受容体の関与が考えられる。従来より網膜では、光情報は主にグルタミン酸が神経伝達物質として情報伝達を担うと考えられてきた。しかしながら、もしP2X受容体がこれに関与するならば、ATPをリガンドとした新たな光情報の伝達機構が存在することとなる。本研究は、網膜における光情報の伝達に関わるP2X受容体サブタイプの種類とこれを有する細胞、及びその伝達機構を明らかにしようというものである。

Outline of Final Research Achievements

ATP acts as a neurotransmitter in the nervous system. All subtypes of P2X receptors (P2X1 - P2X7) have been identified in the mouse retina. However, the types of P2X receptors contributing the signal processing in the retina have not been well elucidated. In the present study, we focused on P2X3 receptors, and investigated the receptor localization and physiological function by immunohistochemistry, in situ hybridization and electrophysiological techniques. We found that P2X3 receptors were detected in amacrine cells and retinal ganglion cells, and the S/N ratio of the firing of retinal ganglion cells was regulated to the appropriate levels.

Academic Significance and Societal Importance of the Research Achievements

本研究は、中枢神経系におけるP2X3受容体の機能の理解に貢献するとともに、眼内でATP濃度の上昇が報告されている緑内障や加齢黄斑変性症などの疾患の新たな治療薬の開発につながることが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (24 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] P2X2 receptors supply extracellular choline as a substrate for acetylcholine synthesis2022

    • Author(s)
      Maruyama Takuma、Mano Asuka、Ishii Toshiyuki、Kakinuma Yoshihiko、Kaneda Makoto
    • Journal Title

      FEBS Open Bio

      Volume: 12 Issue: 1 Pages: 250-257

    • DOI

      10.1002/2211-5463.13332

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of the C‐terminal domain in cell surface localization and G‐protein coupling of mGluR62020

    • Author(s)
      Rai Dilip、Akagi Takumi、Shimohata Atsushi、Ishii Toshiyuki、Gangi Mie、Maruyama Takuma、Wada‐Kiyama Yuko、Ogiwara Ikuo、Kaneda Makoto
    • Journal Title

      Journal of Neurochemistry

      Volume: - Issue: 4 Pages: 837-848

    • DOI

      10.1111/jnc.15217

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Orai1 Channels Are Essential for Amplification of Glutamate-Evoked Ca2+ Signals in Dendritic Spines to Regulate Working and Associative Memory2020

    • Author(s)
      Maneshi Mohammad Mehdi、Toth Anna B.、Ishii Toshiyuki、Hori Kotaro、Tsujikawa Shogo、Shum Andrew K.、Shrestha Nisha、Yamashita Megumi、Miller Richard J.、Radulovic Jelena、Swanson Geoffrey T.、Prakriya Murali
    • Journal Title

      Cell Reports

      Volume: 33 Issue: 9 Pages: 108464-108464

    • DOI

      10.1016/j.celrep.2020.108464

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Interspike intervals within retinal spike bursts combinatorially encode multiple stimulus features.2020

    • Author(s)
      Ishii T. and Hosoya T.
    • Journal Title

      PLoS Comput. Biol.

      Volume: 16 Issue: 11 Pages: e1007726-e1007726

    • DOI

      10.1371/journal.pcbi.1007726

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two Types of Cl Transporters Contribute to the Regulation of Intracellular Cl Concentrations in ON- and OFF-type Bipolar Cells in the Mouse Retina2020

    • Author(s)
      Yin Chengzhu、Ishii Toshiyuki、Kaneda Makoto
    • Journal Title

      Neuroscience

      Volume: 440 Pages: 267-276

    • DOI

      10.1016/j.neuroscience.2020.06.004

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Auxiliary proteins are the predominant determinants of differential efficacy of clinical candidates acting as AMPA receptor positive allosteric modulators.2020

    • Author(s)
      Ishii T., Stolz J.R., and Swanson G.T.
    • Journal Title

      Mol. Pharmacol.

      Volume: 97 Issue: 5 Pages: 336-350

    • DOI

      10.1124/mol.119.118554

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Contribution of P2X3 receptors to visual information processing in the retina.2022

    • Author(s)
      Ishii T., Shimohata A., Suzuki C., Shimogori T., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Acetylcholine release from ON and OFF starburst amacrine cells are regulated by different feedback mechanisms.2022

    • Author(s)
      Gangi M., Maruyama T., Ishii T., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Starburst amacrine cells in the early postnatal development form gap junctions.2022

    • Author(s)
      Maruyama T., Ishii T., Usui S., Shimizu M., and KanedaM.
    • Organizer
      日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 網膜におけるアセチルコリンの役割の検討.2021

    • Author(s)
      Gangi M., Ishii T., and Kaneda M.
    • Organizer
      日本医科大学医学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Modulation of visual information via P2X3 receptors in the mouse retina.2021

    • Author(s)
      Ishii T., Shimohata A., Suzuki C., Shimogori T., Kaneda M.
    • Organizer
      日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] P2X2 receptor-mediated novel acetylcholine synthesis pathway.2021

    • Author(s)
      Maruyama T., Ishii T., Mano A., Kakinuma Y., and Kaneda M.
    • Organizer
      日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Contribution of P2X3 receptors to visual information processing in the retina.2021

    • Author(s)
      Ishii T., Shimohata A., Suzuki C., Shimogori T., Kaneda M.
    • Organizer
      Society for neuroscience
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of P2X2 receptor for acetylcholine synthesis pathway.2021

    • Author(s)
      Maruyama T., Ishii T., Mano A., Kakinuma Y., Kaneda M.
    • Organizer
      Society for neuroscience
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The C-terminal domain is required for mGluR6 cell-surface localization.2021

    • Author(s)
      Shimohata A., Rai D., Akagi T., Ishii T., Gangi M., Maruyama T., Wada-Kiyama Y., Ogiwara I., Kaneda M.
    • Organizer
      Experimental Biology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel transporter-independent acetylcholine synthesis in the mouse retina.2021

    • Author(s)
      Ishii T., Homma K., Maruyama T., Mano A., Kakinuma Y., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Two types of Cl transporters contribute to the intracellular Cl concentrations in ON- and OFF-type bipolar cells in the retina.2021

    • Author(s)
      Yin C., Ishii T., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] The roles of the intracellular C-terminal domain in mGluR6 cell surface localization.2021

    • Author(s)
      Akagi T., Rai D., Shimohata A., Ishii T., Gangi M., Maruyama T., Wada-Kiyama Y., Ogiwara I., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 2種類のClトランスポーターがマウス網膜ON型及びOFF型双極細胞における細胞内Cl濃度の調節に関与する.2020

    • Author(s)
      Yin C., Ishii T., and Kaneda M.
    • Organizer
      日本医科大学医学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Localization of novel ATP permeable channel, CALHM2, in the mouse nervous system.2020

    • Author(s)
      Ishii T., Akagi T., and Kaneda M.
    • Organizer
      日本神経科学大会
    • Related Report
      2020 Research-status Report
  • [Presentation] The analysis of novel ATP release channel in the mitochondria.2020

    • Author(s)
      Ishii T., Akagi T., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Involvement of the C-terminal domain in cell surface expression and G-protein coupling of mGluR6.2020

    • Author(s)
      Shimohata A., Rai D., Akagi T., Ishii T., Gangi M., Maruyama T., Kiyama Y., Ogiwara I., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Contribution of bicarbonate permeability to the reversal potential of GABA responses in bipolar cells of the mouse retina.2020

    • Author(s)
      Yin C., Ishii T., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] The developmental change of gap junction in starburst amacrine cells of the mouse retina.2020

    • Author(s)
      Maruyama T., Ishii T., and Kaneda M.
    • Organizer
      日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 代謝型グルタミン酸6型受容体の細胞膜発現におけるC末端領域の役割.2019

    • Author(s)
      赤木巧、石井俊行、荻原郁夫、金田誠
    • Organizer
      日本医科大学医学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Interspike intervals within retinal spike bursts combinatorially encode oscillatory light sequences.2019

    • Author(s)
      Ishii T. and Hosoya T.
    • Organizer
      日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] NKCC1 and KCC2 determine the surround response of ON- and OFF-bipolar cells in the mouse retina.2019

    • Author(s)
      Yin C., Ishii T., and Kaneda M.
    • Organizer
      日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Asymmetric properties of ON and OFF starburst amacrine cells in the retina.2019

    • Author(s)
      Gangi M., Ishii T., and Kaneda M.
    • Organizer
      日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Roles of the C-terminal domain in cell surface expression of mGluR6.2019

    • Author(s)
      Akagi T., Rai D., Shimohata A., Ishii T., Gangi M., Maruyama T., Ogiwara I. and Kaneda M.
    • Organizer
      日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Store-operated Orai1 channels regulate Ca2+ signaling in dendritic spines, synaptic plasticity, and cognition.2019

    • Author(s)
      Maneshi M., Toth A.B., Ishii T., Radulovic J.M., Swanson G.T., Prakriya M.
    • Organizer
      Society for neuroscience
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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