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Roles of c-kit in functional development of Ca^<2+> release mechanism in smooth muscle cells

Research Project

Project/Area Number 11670094
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKUMAMOTO UNIVERSITY

Principal Investigator

TOKUTOMI Yoshiko  Kumamoto University, School of Medicine, Assistant Professor, 医学部, 助手 (90253723)

Co-Investigator(Kenkyū-buntansha) TOKUTOMI Naofumi  Kumamoto University, School of Medicine, Associate Professor, 医学部, 助教授 (30227582)
NISHI Katsuhide  Kumamoto University, School of Medicine, Professor, 医学部, 教授 (00040220)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordssmooth muscle / Ca^<2+> storage / c-kit / mouse / Patch-clamp technique / fura-2 / ryanodine / caffeine / 平滑筋細胞 / 細胞内Ca^<2+>動態 / Ca^<2+>貯蔵部位 / ryanodine感受性Ca^<2+>ストア
Research Abstract

To clarify the roles of c-kit, a receptor-type tyrosine kinase, in the functional development of smooth muscle cells, we investigated the property of the Ca^<2+>-induced Ca^<2+> release in smooth muscle cells freshly dissociated from gastrointestinal tract of BALB/c mice treated with neutralizing anti-c-kit-monoclonal antibody (ACK2). Under voltage-clamped conditions with the nystatin-perforated patch-clamp technique, c-kit-expressing (c-kit^+) cells developed rhythmic Ca^<2+>-activated Cl^- currents and smooth muscle cells from the control animals developed spontaneous outward currents and caffeine-and carbachol-induced transient outward currents. In smooth muscle cells from the ACK2-treated mice, dysfunction in the ryanodine-sensitive Ca^<2+> storage in the cytoplasm was suggested when tested with caffeine-induced Ca^<2+>-activated K^+ currents and fura-2 fluorometric measurements of intracellular Ca^<2+> concentration. The Ca^<2+> release and caffeine-induced Ca^<2+>-activated K^+ currents in smooth muscle cells from the control animals were ryanodine-sensitive and had great dependence upon the activity of L-type voltage-gated Ca^<2+> channels. In measurements of isometric tension, caffeine-induced relaxation was significantly accelerated in smooth muscles precontracted with high K^+ depolarization or carbachol. Altogether, it is suggested that ryanodine-sensitive Ca^<2+> release is an important modifier of Ca^<2+> homeostasis in the cytoplasm and the contractility of gastrointestinal smooth muscle of mice and that the c-kit^+ cells play important roles in the development of smooth muscle through the rhythmic excitation and Ca^<2+>-fluctuation in the cytoplasm.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Torihashi,S., et al.: "Blockade of Kit Signaling Induces Transdifferentiation of Interstitial Cells of Cajal to a Smooth Muscle Phenotype."Gastroenterology. 117・1. 140-148 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami,M., et al.: "Alkalinization-induced K^+ current of the mouse megakaryocyte."Jpn.J.Pharmacol.. 79・3. 343-350 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokutomi,N. et al.: "The Effects of Mexiletine on the Activity of Neuronal Voltage-gated Na^+ Channels"Jpn.Pharmacol.Ther.. 28・2. 133-141 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokutomi,Y., et al.: "The properties of ryanodine-sensitive Ca^<2+> release in mouse gastric smooth muscle cells."Br.J.Pharmacol.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Torihashi, S., et al.: "Blockade of Kit Signaling Induces Transdifferentiation of Interstitial Cells of Cajal to a Smooth Muscle Phenotype."Gastroenterology. 117(1). 140-148 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami, M., et al.: "Alkalinization-induced K^+ current of the mouse megakaryocyte."Jpn.J.Pharmacol.. 79(3). 343-350 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokutomi N.et al.: "The Effects of Mexiletine on the Activity of Neuronal Voltage-gated Na^+ Channels."Jpn.Pharmacol.Ther.. 28(2). 133-141 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokutomi, Y., et al.: "The properties of ryanodine-sensitive Ca^<2+> release in mouse gastric smooth muscle cells."Br.J.Pharmacol.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Torihashi,S., et al.: "Blockade of Kit signaling induces transdifferentiation of interstitial cells of Cajal to a smooth muscle phenotype."Gastroenterology. 117. 140-148 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murakami,M., et al.: "Alkalinization-induced K^+ current of mouse megakaryocyte."Jpn.J.Pharmacol.. 79. 343-350 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tokutomi,N., et al.: "The effects of mexiletine on the activity of neuronal voltage-gated Na^+ channels."Jpn.Pharmacol.Ther.. 28・2. 133-141 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tokutomi,Y., et al.: "The properties of ryanodine-sensitive Ca^<2+> release in mouse gastric smooth muscle cells."Br.J.Pharmacol.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Torihashi S.,et al: "Blockade of Kit Signaling Induces Transdifferentiation of Interstitial Cells of Cajai to a sweeth Muscle Phenotype"Gestroenterology. 117. 140-148 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Murakami M.,et al: "Alkalinization-induced K^+ current of mouse megakaryocyte"Jpn.J.Pharmacol.. 79. 343-350 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokutomi N.,Nishi K.: "The effects of Mexiletine on the Activity of Neuronal Voltage gated Na^+ Channels"Jpn.Pharmacol.Ther.. 28・2(in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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