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Molecular analysis of the neuropathic pain state using sns-null mutant mice

Research Project

Project/Area Number 13470313
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

FUJIMOTO Yoshinori  Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (30199377)

Co-Investigator(Kenkyū-buntansha) OGATA Nobukuni  Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (80091255)
岡 伸一  広島大学, 医学部・附属病院, 医員
宗重 博  広島大学, 医学部・附属病院, 助教授 (40211601)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2001: ¥7,300,000 (Direct Cost: ¥7,300,000)
Keywordssodium channel / dorsal root ganglion / tetrodotoxin / channel conductance / voltage-clamp / patch-clamp
Research Abstract

Sensory neurons in dorsal root ganglia (DRG) express at least seven isoforms of voltage-gated sodium channel (VGSC) α-subunits. These isoforms show localized distribution within the primary sensory path-way and probably mediate multiple types of sodium currents (I_<Na>) with different kinetic properties, giving rise to fast, slow or persistent I_<Na>s. However, little is known as to which isoform is responsible for a particular I_<Na> in DRG neurons. We have recently identified two types persistent I_<Na>s : one is resistant to tetrodotoxin (TTX) and found exclusively in small DRG neurons (I_<TTX-R/persist>), and the otner is sensitive to TTX and found in medium/large DRG neurons (I_<TTX-S/persist>). Available data suggest that the former is most likely to be mediated by Na_V1.9, while the latter may be mediated by Na_V1.6. To confirm these possibilities, we performed single cell nested RT-PCR combined with concurrent patch clamp recording and investigated the correlation between mRNA … More expression and phenotype of I_<Na> in an identified DRG neuron. I_<TTX-R/persist> was recorded in isolation from small DRG neurons of Na_V1.8-null mutant mice in the presence of TTX. Most of the small neurons, which were associated with Na_V1.9 transcript, manifested I_<TTX-R/persist>, confirming that the isoform mediating I_<TTX-R/persist> is probably Na_V1.9. Unexpectedly, however, Na_V1.9 was evident also in a considerable number of medium/large neurons that were totally devoid of I_<TTX-R/persist>. These results indicate that I_<TTX-R/persist> is not solely dependent on the level of Na_V1.9 transcript. An intriguing finding was that Na_V1.9 transcript was often absent in small DRG neurons from naive mice while the same transcript was evident in most of the small DRG neurons from mutants. Expression of Na_V1.6 transcript was demonstrated in a considerable portion of the medium/large neurons from both naive and mutant mice. However, these neurons did not consistently manifest I_<TTX-S/persist> suggesting that I_<TTX-S/persist> may not be carried by Na_V1.6. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Ogata, N.: "Molecular diversity of structure and function of the voltage-gated Na^+ channels"Jap. J. Pharmacol.. 88. 1-13 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogata, N.: "New perspectives on the structure and function of the sodium channel multigene family"Curr. Med. Chem.. 2. 59-81 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 緒方宣邦: "痛覚伝導における電位依存性ナトリウムチャネルの新しい役割持続性Na電流の細胞特異的発現とその機能"ペインクリニック. 23. 1245-1257 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 緒方宣邦: "テトロドトキシン非感受性ナトリウムチャネルの痛覚制御機構における役割"日本ペインクリニック学会誌. 10. 1-12 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohishi, Y.: "Use-dependent unblocking of the transient K+ current by 4-aminopyridine in rat dorsal root ganglia"J. Pharmacol. Sci.. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 赤池紀扶: "脳機能の解明「生命科学の主潮流」"ガイア出版会. 571 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogata, N.: "Molecular diversity of structure and function of the voltage-gated Na^+ channels"Jap. J. Pharmacol.. 88. 365-377 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogata, N.: "New perspectives on the structure and function of the sodium channel multigene family"Curr. Med. Chem.. 2. 59-81 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogata, N.: "The role of voltage-gated sodium channels in pain sensation : functional expression of the persistent sodium currents in sensory neurons (Japanese)"Pain Clinic.. 23. 1245-1257 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ogata, N.: "Functional roles of the tetrodotoxin-resistant sodium channel in pain sensation (Japanese)"Journal of the Japan Society of Pain Clinicians. 10. 1-12 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohishi, Y.: "Use-dependent unblocking of the transient K^+ current by 4-aminopyridine in rat dorsal root ganglia"J. Pharmacol. Sci.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maruyama, H: "The role of tetrodotoxin-resistant sodium channels in pain sensation"Pain Res.. 16・2. 51-56 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 緒方 宣邦: "SNSノックアウトマウスを用いた痛みの研究"日本臨床. 59・9. 1688-1697 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogata, N.: "Molecular diversity of structure and function of the voltage-gated Na^+ channels"Jap. J. Pharmacol.. 88・4. 1-13 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogata, N.: "New perspectives on the structure and function of the sodium channel multigene family"Curr. Med. Chem.. 2・1. 59-81 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 緒方宣邦: "痛覚伝導における電位依存症ナトリウムチャネルの新しい役割 持続性Na電流の細胞特異的発現とその機能"ペインクリニック. 23・9. 1245-1257 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 緒方宣邦: "ナトリウムチャネルと痛み -後根神経節における持続型ナトリウムチャネル-"脳21. 6・1. 22-33 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 緒方宣邦: "テトロドトキシン非感受性ナトリウムチャネルの痛覚制御機構における役割"日本ペインクリニック学会誌. 10・1. 1-2 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohishi, Y.: "Use-dependent unblocking of the transient K+ current by 4-aminopyridine in rat dorsal root ganglia"J. Pharmacol. Sci.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maruyama, H.: "Characterization of the tetrodotoxin-resistant Na+ channel, NaV1.9, in mouse dorsal root ganglia"J. Physiol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 赤池紀扶: "脳機能の解明「生命科学の主潮流」"ガイア出版社. 571 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maruyama, H: "The role of tetrodotoxin-resistant sodium channels in pain sensation"Pain Res.. 16・2. 51-56 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 緒方宣邦: "SNSノックアウトマウスを用いた痛みの研究"日本臨床. 59・9. 1688-1697 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogata, N.: "Molecular diversity of structure and function of the voltage-gated Na^+ channels"Jap. J. Pharmacol.. 88・4. 1-13 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogata, N.: "New perspectives on the structure and function of the sodium channel multigene family"Curr, Med. Chem.. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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