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Mechanism of expression of voltage-gated sodium and calcium channels

Research Project

Project/Area Number 16390056
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionNational Institute of Natural Sciences Okazaki Research Facilities

Principal Investigator

OKAMURA Yasushi  National Institute of Natural Sciences, Okazaki Research Facilities, Okazaki Institute for Integrative Bioscience, Professor, 岡崎総合バイオサイエンスセンター, 教授 (80201987)

Co-Investigator(Kenkyū-buntansha) KUKITA Fumio  National Institute for Physiological Sciences, Assistant Professor, 生理学研究所, 助手 (40113427)
IWASAKI Hirohide  National Institute for Physiological Sciences, Center for Brain Experiment, Assistant Professor, 生理学研究所・脳機能計測センター, 助手 (30342752)
EBIHARA Tatsuhiko  AIST, Researcjer, 産業技術総合研究所・脳神経情報研究部門, 研究員 (00344119)
HAYASAKA Kiyoshi  Yamagata Univertisy, Pediatrics, Professor, 医学部発達生体崩御学講座小児医学化学分野, 教授 (20142961)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
Keywordsion channel / voltage sensor / inactivation / persistent sodium current / sodium channel / ankyrin / PTEN / phosphatase
Research Abstract

Ankyrin-G, a modular protein, plays a critical role in clustering voltage-gated sodium channels (Nav channels) in nodes of Ranvier and initial segments of mammalian neurons. However, direct effects of ankyrin-G on electrophysiological properties of Nav channels remai elusive. In this study, we explored whether ankyrin-G has a role in modifying gating properties of the neuronal Nav1.6 channel that is predominantly localized at nodes of Ranvier and initial segments. TsA201 cells transfected with the human Nav1.6 cDNA alone exhibited significant persistent sodium current (Ina-p). On the other hand, Ina-p was barely detected upon co-expression with ankyrin-G. Ankyrin-B, another ankyrin, did not show such an effect. Expression of chimeras between the two isofrms of ankyrin suggests that the membrane-binding domain of ankyurin-G is critical for reducing the Ina-p of Nav1.6. These results suggest that ankyrin-G regulates neuronal excitability not only through clustering Nav channels but also … More by directly modifying their channel gating. Changes is membraine potential affect ion channels, and transporters, which then alter intracellular chemical conditions. Ohter signaling pathways coupled to membrane potential have been suggested but their underlying mechanism are unknown. We have identified a novel protein from the ascidian Ciona intestinalis which has a transmembrane voltage sensing domain homologous to the S1-S4 segments of voltage-gated channels and a cytoplasmic domain similar to phosphatase and tension homologue (PTEN). This protein, named Ci-VSP (voltage-sensor containing phosphatase), displays channel-like "gating" currents and directly translates changes in membrane potential into the turnover of phosphoinositides. The activity of the phosphoinositide phosphatase in Ci-VSP is tuned within a physiological range of membrane potential. Immunocytochemical studies show that Ci-VSP is expressed in Ciona sperm tail membranes, suggesting a role in sperm function or morphology. Our data demonstrate that voltage sensing can function beyond channel proteins and thus more ubiquitously than previously appreciated. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report

Research Products

(43 results)

All 2006 2005 2004 Other

All Journal Article (34 results) Book (3 results) Patent(Industrial Property Rights) (6 results)

  • [Journal Article] A voltage sensor domain protein is a voltage-gated proton channel2006

    • Author(s)
      M.Sasaki
    • Journal Title

      Science 312

      Pages: 589-592

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 膜電位を感じて活性を変化させるイノシトールリン脂質脱リン酸化酵素2006

    • Author(s)
      岡村康司
    • Journal Title

      蛋白質核酸酵素 51・1

      Pages: 18-26

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 電位センサーの動作原理と電位感受性酵素VSP2006

    • Author(s)
      岡村康司
    • Journal Title

      細胞工学 25・3月号

      Pages: 231-235

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A voltage sensor-domain protein is a voltage-gated proton channel2006

    • Author(s)
      Sasaki, M., Takagi, M., Okamura Y.^*
    • Journal Title

      Science 312

      Pages: 589-592

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] New role of voltage sensor-voltage-regulated phosphatase recently identified from assician genome2006

    • Author(s)
      Y.Okamura
    • Journal Title

      Protein, Nucleic Acid and Enzyme 51

      Pages: 18-26

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Voltage sensor in ion channel and phosphatase2006

    • Author(s)
      Y.Okamura
    • Journal Title

      Cell Technology 25.March

      Pages: 231-235

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A voltage sensor domain protein is a voltage-gated proton channel2006

    • Author(s)
      M.Sasaki
    • Journal Title

      Science (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 電位センサーの動作原理と電位感受性酵素VSP2006

    • Author(s)
      岡村康司
    • Journal Title

      標準生理学(イオンチャンルの発現制御機構) 25.3月号

      Pages: 231-235

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Early specification of ascidian larval motor neurons2005

    • Author(s)
      Y.Katsuyama, T.Okada, J.Matsumoto, Y.Ohtsuka, T.terashima, Y.OKAMURA
    • Journal Title

      Dev.Biol 278

      Pages: 310-322

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of Nav channels in sensory neuron2005

    • Author(s)
      M.Chahine, K.Vijayaragavan, Y.OKAMURA
    • Journal Title

      Trends Pharmacol.Sci. 26・10

      Pages: 496-502

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor2005

    • Author(s)
      Y.Murata
    • Journal Title

      Nature 435・7046

      Pages: 1239-1243

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Comprehensive analysis of the ascidian genome reveals novel insights into the molecular evolution of ion channel genes2005

    • Author(s)
      Y.Okamura
    • Journal Title

      Physiol Genomics 22・3

      Pages: 269-282

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] GABAergic synaptic transmission modulates swimming in the ascidian larva2005

    • Author(s)
      E.R.Brown
    • Journal Title

      Eur.J.Neurosci. 22・10

      Pages: 2541-2548

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Tight junctions in Schwann cells of peripheral myelinated axons : a lesson from claudin-19-deficient mice2005

    • Author(s)
      T.Miyamoto
    • Journal Title

      J Cell Biol 169・3

      Pages: 527-538

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] イオンチャネル遺伝子から見た生理機能の進化2005

    • Author(s)
      岡村康司
    • Journal Title

      海洋 41・号外

      Pages: 61-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] イオンの出入りを介さず膜電位シグナルを伝えるタンパク質Ci-VSP2005

    • Author(s)
      岩崎広英
    • Journal Title

      実験医学 23・19

      Pages: 2942-2944

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor2005

    • Author(s)
      Y.Murata, H.Iwasaki, M.Sasaki, K.Inaba, Y.Okamura^*
    • Journal Title

      Nature 435

      Pages: 1239-1243

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Early specification of ascidian larval motor neurons2005

    • Author(s)
      Y.Katsuyama^*, H.Okada, J.Matsumoto, Y.Ohtsuka, T.Terashima, Y.Okamura
    • Journal Title

      Develop.Biol. 278

      Pages: 310-322

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Comprehensive analysis of the ascidian genome reveals novel insights into the molecular evolution of ion channel genes2005

    • Author(s)
      Y.Okamura^*, A.Nishino, Y.Murata, K.Nakajo, H.Iwasaki, Y.Ohtsuka, M.Tanaka-Kunishima, N.Takahashi, Y.Hara, T.Yoshida, M.Nishida, H.Okado, H.Watari, l.A.Meinertzhagen, N.Satoh, K.Takahashi, Y.Satou, Y.Okada, Y.Mori
    • Journal Title

      Physiol.Genomics 22

      Pages: 269-682

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] GABAergic synaptic transmission modulates swimming in the ascidian larva2005

    • Author(s)
      Brown E.R.^*, Nishino A., Bone Q., Meinertzhagen l.A., Okamura, Y.
    • Journal Title

      Eur.J.Neurosci. 22

      Pages: 2541-2548

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tight junctions in Schwann cells of peripheral myelinated axons : a lesson from claudin-19-deficient mice2005

    • Author(s)
      T.Miyamoto, K.Morita, D.Takemoto, K.Takeuchi, Y.Kitano, T.Miyakawa, K.Nakayama, Y.Okamura, H.Sasaki, Y.Miyachi, M.Furuse, S.Tsukita^*
    • Journal Title

      J.Cell Biol. 169

      Pages: 527-538

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of Nay channels in sensory neurons2005

    • Author(s)
      Chahine M^*, Ziane R, Vijayaragavan K, Okamura Y.
    • Journal Title

      Trends in Pharmacological Sciences 10

      Pages: 496-502

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Volatge-regulated phosphatase : CI-VSP2005

    • Author(s)
      H.Iwasaki
    • Journal Title

      Experimental Medicine 23

      Pages: 2942-2944

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of neuronal ion channels2005

    • Author(s)
      Y.Okamura
    • Journal Title

      Brain Science Review 2005 (Kubapro)

      Pages: 23-26

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] イオンの出入りを介さず膜電位シグナルを伝えるタンパク質Ci-VSP2005

    • Author(s)
      山崎広英
    • Journal Title

      実験医学 23・19

      Pages: 2942-2944

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Early specification of ascidian larval motor neurons2005

    • Author(s)
      Y.Katsuyama, T.Okada, J.Matsumoto, Y.Ohtsuka, T.Terashima, Y.OKAMURA
    • Journal Title

      Dev.Biol. 278

      Pages: 310-322

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of transient outward currents coupled with Ca^<2+>-induced Ca^<2+> release mediates oscillatory membrane potential in ascidi2004

    • Author(s)
      K.Nakajo K, Y.OKAMURA
    • Journal Title

      J.Neurophysiol. 92

      Pages: 1056-1066

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] The neurobiology of the ascidian tadpole larva.2004

    • Author(s)
      I.A.Meinertzhagen, P.Lemaire, Y.OKAMURA
    • Journal Title

      Annu.Rev.Neurosci. 27

      Pages: 453-485

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Development of transient outward currents coupled with Ca2+-induced Ca2+ release mediates oscillatory membrane potential in ascidian Muscle Cells2004

    • Author(s)
      K.Nakajo^*, Y.Okamura
    • Journal Title

      J.Neurophysiol 92

      Pages: 1056-1066

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The neurobiology of the ascidian tadpole larva2004

    • Author(s)
      I.A.Meinertzhagen^*, P.Lemaire, Y.Okamura
    • Journal Title

      Annu.Rev.Neurosci 27

      Pages: 453-485

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Evolution of chordate physiological functions viewed from ion channel genes

    • Author(s)
      Y.Okamura
    • Journal Title

      KAIYO Monthly 41

      Pages: 61-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tight junctions in Schwann cells of peripheral myelinated axons : a lesson from claudin-19-deficient mice

    • Author(s)
      T.Miyamoto, K.Morita D.Takemoto, K.Takeuchi Y.Kitano, T.Miyakawa, K.Nakayama Y.OKAMURA, H.Sasaki, Y.Miyachi, M.Furuse, S.Tsukita
    • Journal Title

      J.Cell.Biol. (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of Nay channels in sensory neuron

    • Author(s)
      M.Chahine, K.Vijayaragavan, Y.OKAMURA
    • Journal Title

      Trends Pharmacol.Sci. (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activity of a phosphoinositide phosphatase is coupled to its intrinsic voltage-dependence

    • Author(s)
      Y.Murata, H.Iwasaki, M.Sasaki, K.Inaba, Y.OKAMURA
    • Journal Title

      Nature (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Book] イオンチャネルの発現制御機構2005

    • Author(s)
      岡村康司
    • Total Pages
      1176
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Book] 「神経系におけるイオンチャネル発現制御機構」ブレインサイエンスレビュー20052005

    • Author(s)
      岡村 康司
    • Publisher
      クバプロ
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Regulation of ion channel expression2005

    • Author(s)
      Y.Okamura
    • Total Pages
      1176
    • Publisher
      Igakushoin
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 新規イオンチャネル様ポリペプチドおよびその利用2005

    • Inventor(s)
      岡村康司
    • Industrial Property Rights Holder
      国立大学法人京都大学自然科学機構
    • Filing Date
      2005-05-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 電位活性化型プロトンチャネルを構成するタンパク質およびその利用法2005

    • Inventor(s)
      岡村康司
    • Industrial Property Rights Holder
      自然科学研究機構
    • Filing Date
      2005-09-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 新規イオンチャネル様ポリペプチドおよびその利用2005

    • Inventor(s)
      岡村康司
    • Industrial Property Rights Holder
      国立大学法人京都大学, 自然科学研究機構
    • Filing Date
      2005-05-13
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 電位活性化型プロトンチャネルを構成するタンパク質およびその利用法2005

    • Inventor(s)
      岡村康司
    • Industrial Property Rights Holder
      自然科学研究機構
    • Filing Date
      2005-09-05
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規イオンチャネル様ポリペツチドおよびその利用2004

    • Inventor(s)
      岡村康司, 佐藤炬行, 岩崎広英, 村田喜理
    • Industrial Property Rights Holder
      岡村康司, 佐藤炬行, 岩崎広英, 村田喜理
    • Filing Date
      2004-11-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 新規イオンチャネル様ポリプペチドおよびその利用2004

    • Inventor(s)
      岡村 康司, 佐藤 矩行, 岩崎 広英, 村田 喜理
    • Industrial Property Rights Holder
      岡村 康司, 佐藤 矩行, 岩崎 広英, 村田 喜理
    • Filing Date
      2004-11-16
    • Related Report
      2004 Annual Research Report

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Published: 2004-03-31   Modified: 2016-04-21  

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