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Mechanism underlying polarized subcellular distribution of Ca channels and its neurobiological significance.

Research Project

Project/Area Number 14380362
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKYOTO UNIVERSITY (2003)
Okazaki National Research Institutes (2002)

Principal Investigator

MORI Yasuo  Kyoto University Graduate School of Engineering, Professor, 工学研究科, 教授 (80212265)

Co-Investigator(Kenkyū-buntansha) NISHIDA Motohiro  Kyushu University of Graduate School of Pharmaceutical Sciences, Lecturer, 薬学研究院, 講師 (90342641)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2003: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
Keywordsreceptor activated channel / Ca2+ signal / smooth muscle / endoplasmic reticulum / 薬理学 / ノックアウト
Research Abstract

Two mechanisms that link presynaptic defects to postsynaptic aspects of neuronal differentiation and maturation have been revealed. Firstly, in N-type, Ca^<2+> channel-deficient mice we created, positive, regulation by automic nervous system was ablated. This is reasonable, considering that noradrenalin release from presynaptic terminal is predominantly controlled by N-type channels in wild-type mice. However, interestingly, cardiac contraction, vascular constriction, and sensitivity of receptors to their agonists were upregulated in the mutant mice. Secondly, we compared fundamental properties of excitatory synaptic transmission in the cerebellum and roles of Ca^<2+> channel subtypes among wild-type control, tottering (tg) and rolling Nagoya (tg^<rol>) that carry mutations in the P/Q-type Ca^<2+> channel α_<1A> (Cav2.l) subunit gene. The EPSC amplitude of the climbing fiber-Purkinje cell (CF-PC) synapses was preserved in tg, and it was even increased in tg^<rol>, which was associated … More with altered properties of the postsynaptic glutamate receptors. The climbing fiber mediated EPSC was more dependent on other Ca^<2+> channel subtypes in mutant mice, suggesting that such compensatory mechanisms contribute to maintaining the CF-PC synaptic transmission virtually intact. Thus, presynaptic Ca^<2+> channels control postsynaptic excitability and function and thereby regulate differentiation and maturation synapses. We showed that G protein-coupled, metabotropic glutamate receptor subtype 1 (mGluR1) and P/Q-type Cav2.1 are colocalized at dendrites of cerebellar Purkinje neurons and form the heteromeric assembly in both the brain and heterologously expressing COS-7 cells. mGluR1 inhibited Cav2.1-mediated [Ca^<2+>]i increases and Ba2+ currents in HEK 293 cells expressing Cav2.1 with auxiliary alpha2/delta and beta1 subunits, respectively, in a ligand-independent manner and was enhanced by pre activation of mGluR1 in a ligand-dependent manner. Furthermore, in dihdropyridine (DHP)-sensitive L-type Ca^<2+> channel Cav1.2 (α1c), Ser1142 was the recognition site for both the DHP agonist BAYk8644 and Phosphatase inhibited by okadaic acid. This suggests that upregulation of L-type channels by DHP agonist and that by Ser phophorylation are mediated by a common mechanism involving Ser1142. Finally, we carried out two-hybrid screening using the β4 subunit as a bate to isolate a clone encoding the protein regulating fusion of synaptic vesicles. Functional and molecular characterization of the protein is under way. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (47 results)

All Other

All Publications (47 results)

  • [Publications] Dos Santos RG, Van Renterghem C, Martin-Moutot N, Mansuel P, Sampieri F, Diniz C, Mori Y, De Lima M-E, Seagar M: "ω Phoneutria nigriventer IIA blocks the Ca_v2 family of calcium channels and interacts with ω conotoxin binding sites."J.Biol.Chem.. 277. 13856-13862 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsushita K, Wakamori M, Rhyu IJ, Arii T, Oda S, Mori Y, Imoto K: "Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca^<2+> channel mutant mice."J.Neurosci.. 22. 4388-4398 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato K, Wakamori M, Mori Y, Imoto K, Kitamura K: "Inhibitory effects of cilnidipine on peripheral and brain N-type Ca^<2+> channels expressed in BHK cells."Neurophamacol. 42. 1099-1108 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Cornet V, Bichet D, Sandoz G, Marty I, Brocard J, Bourinet E, Mori Y, Villaz M, De Waard M.: "Multiple ER retention determinants control the cell surface targeting of voltage-dependent P/Q calcium channels."Eur.J.Neurosci.. 16. 883-895 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikkath J, Felix R, Ahern C, Chen CC, Mori Y Song I, Shin H-S, Coronado R, Campbell KP: "Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel α_12.1 subunit."FEBS Lett.. 532. 300-308 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori Y, Nishida M, Ino M, Yoshinaga T, Niidome T, Sawada K: "Mice lacking the 1B subunit (Ca_v 2.2) reveals a predominant role of N-type Ca^<2+> channels in the sympathetic regulation of circulatory system."Trends Cardiovasc.Med.. 12. 270-274 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 森泰生, 吉田卓史, 原雄二: "脳における多様な非選択性カチオンチャネル"生体の科学(特集 一価イオンチャネル). 53. 316-322 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 西田基宏, 森泰生: "ナトリウムポンプ"分子生物学・免疫学キーワード辞典 第2版(医学書院). 2. 605-606 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 森泰生, 西田基宏: "カルシウムチャネル"分子生物学・免疫学キーワード辞典 第2版(医学書院). 2. 242-243 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 西田基宏, 森泰生: "カルシウムチャネル括抗剤"分子生物学・免疫学キーワード辞典 第2版(医学書院). 2. 243-244 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Erxleben C, Allegria-Gomez C, Darden, Mori Y, Birnbaumer L, Armstrong DL: "Modulation of cardiac Cav 2.1 channels by BAYk8644 and Okadaic acid Requires S1142 in the domain III pore loop."Proc.Natl.Acad.Sci.USA. 100. 2929-2934 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu S, Shiota K, Yamamoto S, Miyasaka Y, Ishii M, Watabe T, Nishida M, Mori Y, Yamamoto T, Kiuchi Y: "Hydrogen peroxide stimulates tetrahydrobiopterin synthesis through the induction of GTP-cyclohydrolase I and increases nitric oxide synthase activity in vascular endothelial cells."Free Radic.Biol.Med.. 34. 1343-1352 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugimoto K, Mori Y, Makino K, Ohkubo K, Morii T: "Functional Reassembly of a Split PH Domain."J.Am.Chem.Soc.. 125. 5000-5004 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitano J, Nishida M, Itsukaichi Y, Minami I, Ogawa M, Hirano T, Mori Y, Nakanishi S: "Direct interaction and functional coupling between metabotropic receptor type 1 and voltage-sensitive Ca_v2.1 Ca^<2+> channel"J.Biol.Chem.. 278. 25101-25108 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishida M, Sugimoto K, Hara Y, Mori E, Morii T, Kurosaki T, Mori Y: "Amplification of receptor signaling by Ca^<2+> entry-mediated translocation and activation of phospholipase Cγ2 in B lymphocytes."EMBOJ.. 22. 4677-4688 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori Y, Itsukaichi Y, Nishida M, Oka H: "Ca^<2+> channel mutations and associated diseases"In "Ca channel pharmacology book" (ed. McDonough S, Kluwer Academic/Plenum Publishers). 303-330 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugimoto K, Nishida M, Otsuka M, Ohkubo K, Mori Y, Morii T: "Novel real time sensors to quantitatively assess in vivo inositol 1,4,5-trisphosphate production in intact cells."Chem.Biol.. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Dos Santos RG, Van Renterghem C, Martin-Moutot N, Mansuel P, Sampieri F, Diniz C, Mori Y, De Lima M-E, Seagar M: "ω Phoneutria nigriventer 11A toxin blocks the Ca2 family of calcium channels and interacts with ω conotoxin binding sites."J.Biol.Chem.. 277. 13856-13862 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsushito K, Wakamori M, Rhyu IJ, Arii T, Oda S, Mori Y, Imoto K: "Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca^<2+> channel mutant mice."J.Neurosci.. 22. 4388-4398 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato K, Wakamori M, Mori Y, Imoto K, Kitamura K: "Inhibitory effects of cilnidipine on peripheral and brain N-type Ca^<2+> channels expressed in BHK cells."Neuropharmacol.. 42. 1099-1108 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Cornet V, Bichet D, Sandoz G, Marty I, Brocard J, Bourinet E, Mori Y, Villaz M, De Waard M.: "Multiple ER retention determinants control the cell surface targeting of voltage-dependent P/Q calcium channels."Eur.J.Neurosci.. 16. 883-895 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikkath J, Felix R, Ahern C, Chen CC, Mori Y, Song I, Shin H-S, Coronado R, Campbell KP: "Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel ・1^<2.1> subunit."FEBS Lett.. 532. 300-308 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Erxleben C, Allegria-Gomez C, Darden, Mori Y, Birnbaumer L, Armstrong DL: "Modulation of cardiac Ca_V 2.1 channels by BAYk8644 and Okadaic acid requires S1142 in the domain III pore loop."Proc.Natl.Acad.Sci.USA. 100. 2929-2934 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu S, Shiota K, Yamamoto S, Miyasaka Y, Ishii M, Watabe T, Nishida M, Mori Y, Yamamoto T, Kiuchi Y: "Hydrogen peroxide stimulates tetrahydrobiopterin synthesis through the induction of GTP-cyclohydrolase I and increases nitric oxide synthase activity in vascular endothelial cells."Free Radic.Biol.Med.. 34. 1343-1352 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugimoto K, Mori Y, Makino K, Ohkubo K, Morii T: "Functional Reassembly of a Split PH Domain."J.Am.Chem.Soc.. 125. 5000-5004 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitano J, Nishida M, Itsukaichi Y, Minami I, Ogawa.M, Hirano T, Mori Y, Nakanishi S: "Direct interaction and functional coupling between metabotropic receptor type 1 and voltage-sensitive Ca_V2.1 Ca^<2+> channel."J.Biol.Chem.. 27. 25101-25108 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishida M, Sugimoto K, Hara Y, Mori E, Morii T, Kurosaki T, Mori Y: "Amplification of receptor signaling by Ca^<2+> entry-mediated translocation and activation of phospholipase C・2 in B lymphocytes."EMBO J.. 22. 4677-4688 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugimoto K, Nishida M, Otsuka M, Ohkubo K, Mori Y, Morii T: "Novel real time sensors to quantitatively assess in vivo inositol 1,4,5-trisphosphate production in intact cells."Chem.Biol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori Y, Nishida M, Ino M, Yoshinaga T, Niidome T, Sawada K: "Mice lacking the ・1B subunit (Ca_V 2.2) reveals a predominant role of N-type Ca^<2+> channels in the sympathetic regulation of circulatory system."Trends Cardiovasc.Med.. 12. 270-274 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori Y, Itsukaichi Y, Nishida M, Oka H: "Ca^<2+> channel mutations and associated diseases"Ca channel pharmacology book (ed. McDonough S, Kluwer) (Academic/Plenum "Publishers)Calcium Channel Pharmacology. 303-330 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Erxleben C, Allegria-Gomez C, Darden, Mori Y, Birnbaumer L, Armstrong DL: "Modulation of cardic Ca_v 2.1 channels by BAYk8644 and Okadaic acid Requires S1142 in the domain III pore loop"Proc.Natl.Acad.Sci.USA. 100. 2929-2934 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimizu S, Shiota K, Yamamoto S, Miyasaka Y, Ishii M, Watabe T, Nishida M, Mori Y, Yamamoto T, Kiuchi Y: "Hydrogen peroxide stimulates tetrahydrobiopterin synthesis through the induction of GTP-cyclohydrolase I and increases nitric oxide synthase activity in vascular endothelial cells"Free Radic.Biol.Med.. 34. 1343-1352 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugimoto K, Mori Y, Makino K, Ohkubo K, Morii T: "Functional Reassembly of a Split PH Domain"J.Am.Chem.Soc.. 1215. 5000-5004 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kitano J, Nishida M, Itsukaichi Y, Minami I, Ogawa M, Hirano T, Mori Y, Nakanishi S: "Direct interaction and functional coupling between metabotropic receptor type 1 and voltage-sensitive Ca_v2.1 Ca^<2+> channel"J.Biol.Chem.. 278. 25101-25108 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishida M, Sugimoto K, Hara Y, Mori E, Morii T, Kurosaki T, Mori Y: "Amplification of receptor signaling by Ca^<2+> entry-mediated translocation and activation of phospholipase Cγ2 in B lymphocytes"EMBO J.. 22. 4677-4688 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugimoto K, Nishida M, Otsuka M, Ohkubo K, Mori Y, Morii T: "Novel real time sensors to quantitativily assess in vivo inositol 1,4,5-trisphosphate production in intact cells"Chem.Biol.. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Dos Santos RG, Van Renterghem C, Martin-Moutot N, Mansuel P, Sampieri F, Diniz C, Mori Y, De Lima M-E, Seagar M: "・Phoneutria nigriventer IIA toxin blocks the Ca_v2 family of calcium channels and interacts with・conotoxin binding sites"J. Biol. Chem.. 277. 13856-13862 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsushita K, Wakamori M, Rhyu IJ, Arii T, Oda S, Mori Y, Imoto K: "Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca^<2+> channel mutant mice"J. Neurosci.. 22. 4388-4398 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato K, Wakamori M, Mori Y, Imoto K, Kitamura K: "Inhibitory effects of cilnidipine on penpheral and brain N-type Ca^<2+> channels expressed in BHK cells"Neuropharmacol. 42. 1099-1108 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Cornet V, Bichet D, Sandoz G, Marty I, Brocard J, Bourinet E, Mori Y, Villaz M, De Waard M.: "Multiple ER retention determinants control the cell surface targeting of voltage-dependent P/Q calcium channels"Eur. J. Neurosci.. 16. 883-895 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arikkath J, Felix R, Ahern C, Chen CC, Mori Y, Song I, Shin H-S, Coronado R, Campbell KP: "Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel α_12.1 subunit"FEBS Lett.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori Y, Nishida M, Ino M, Yoshinaga T, Niidome T, Sawada K: "Mice lacking the α_<1B> subunit (Ca_v 2.2) reveals a predominant role of N-type Ca^<2+> channels in the sympathetic regulation of circulatory system"Trends Cardiovasc. Med.. 12. 270-274 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori Y, Itsukaichi Y, Nishida M, Oka H: "Ca^<2+> channel mutations and associated diseases"In "Ca channel pharmacology book" (ed. McDonough S, Kluwer Academic/ Publishers). (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 森泰生, 吉田卓史, 原雄二: "脳における多様な非選択性カチオンチャネル"生体の科学(特集 一価イオンチャネル). 53. 316-322 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 西田基宏, 森泰生: "ナトリウムポンプ"分子生物学・免疫学キーワード辞典 第2版(、医学書院). (in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 森泰生, 西田基宏: "カルシウムチャネル"分子生物学・免疫学キーワード辞典 第2版(医学書院). (in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 西田基宏, 森泰生: "カルシウムチャネル拮抗剤"分子生物学・免疫学キーワード辞典 第2版(医学書院). (in press). (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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