Studies on molecular mechanisms of ion channel clustering at the nodes of Ranvier.

• Project/Area Number: 14580749
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: BABA Hiroko Tokyo University of Pharmacy and Life Science, School of pharmacy, Professor, 薬学部, 教授 (40271499)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Akiko HAYASHI,Akiko, 薬学部, 助手 (90232090) ; YAMAGUCHI Yoshihide YAMAGUCHI,Yoshihide, 薬学部, 講師 (50311832)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,100,000 (Direct Cost: ¥3,100,000); Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: voltage-gated sodium channel / voltage-gated potassium channel / the nodes of Ranvier / myelin / myelinated nerve fiber / sulfatide / oligodendrocyte / shcwann cell / サルファチド

Research Abstract

We have studied the molecular mechanisms of characteristic localizations of voltage-gated ion channels in myelinated axons : The followings are the results in the present study.1) We analyzed protein complex with myelin protein CD9, which contributed to the formation of paranodal junction(PJ)using immunoprecipitation.As a result, CD9 formed a complex with membrane proteins such as integrin, claudini, MOG as well as CD81.2)We examined the influence of PJ on switching of sodium channel subtypes using the sulfatide-deficient(CST KO)mouse.This mutant displayed disruption of PJ and altered nodal lengths and channel distributions.The results in the mutant CNS suggested that PJ formation is necessary for complete replacement of nodal Nav1.2 to Nav1.6 during development as well as maintenance of Nav1.6 clusters at the nodes.3) Such subtype abnormality was not cbserved in the PNS, where PJ disruption was observed.Thus, PJ significantly influences the retention of Nav1.6 in the node, which is followed by disorganization of nodal structures.However, its importance may differ between the central and peripheral nervous system.The molecules those bind to CD9 may have some roles for the formation of PJ and maintenance of ion channels in the nodes.

Research Products

• [Publications] Ishibashi T, Dupree JL, Ikenaka K, Hirahara Y, Honke K, Peles E, Popko B, Suzuki K, Nishino H, Baba H.: "A myelin ealactolipid, sulfatide, is essential for maintenance of ion channels on mvelmated axon but not essential for initial cluster formation."Journal of Neurochemical Research. 22・15. 6507-6514 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ishibashi T, Ikenaka K, Shimizu T, Kagawa T, Baba H: "Initiation of sodium channel clustering at the node of Ranvier in the mouse optic nerve."Neurochem Res. 28. 117-125 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ayaka Suzuki, Tomiko Hoshi, Tomoko Ishibashi, Akiko Hayashi, Yoshihide Yamaguchi, Hiroko Baba: "Paranodal axoglial junction is required for the maintenance of the Nav1.6-type sodium channel in the node of Ranvier in the optic nerves but not in peripheral nerve fibers in the sulfatide-deficient mice"Glia. 46・3. 274-283 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ishibashi T, Ikenaka K, Shimizu T, Kagawa T, Baba H.: "Initiation of sodium channel clustering at the node of Ranvier in the mouse optic nerve."Neurochem Res.. 28(1). 117-125 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishibashi T, Ding L, Ikenaka K, Inoue Y, Miyado K, Mekada E, Baba H.: "Tetraspanin protein CD9 is a novel paranodal component regulating paranodal junctional formation."J Neurosci.. 24(1). 96-102 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Suzuki A, Hoshi T, Ishibashi T, Hayashi A, Yamaguchi Y, Baba H.: "Paranodal axoglial junction is required for the maintenance of the Nav1.6-type sodium channel in the node of Ranvier in the optic nerves but not in peripheral nerve fibers in the sulfatide-deficient mice."Glia.. 46(3). 274-283 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishibashi T, Ikenaka K, Shimizu T, Kagawa T, Baba H.: "Initiation of sodium channel clustering at the node of Ranvier in the mouse optic nerve."Neurochem Res. 28. 117-125 (2003)
• [Publications] Tomoko Ishibashi: "A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation"Journal of Neuroscience. 22・15. 6507-6514 (2002)
• [Publications] Tomoko Ishibashi: "Initiation of sodium channel clustering at the node of Ranvier in the mouse optic nerve"Neurochemical Research. 28・1. 117-125 (2003)