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Cross-link of signal transduction and channel function diabetic neuropathy

Research Project

Project/Area Number 09670652
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionShiga University of Medical Science

Principal Investigator

YASUDA Hitoshi  Shiga University of Medical Science, Third Department of Medicine, Assistant Professor, 医学部, 講師 (80135467)

Co-Investigator(Kenkyū-buntansha) YOSHIHIKO Nishio  Shiga University of Medical Science, Third Department of Medicine, Instructor, 医学部, 助手 (40281084)
TERADA Masahiko  Shiga University of Medical Science, Department of General Medicine, Associate Professor, 医学部, 助教授 (00227521)
KITASATO Hiroshi  Shiga University of Medical Science, Second Department of Physiology, Ex-Professor, 医学部, 名誉教授 (20079700)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsdorsal root ganglion / tetrodotoxin-resistant / NaィイD1+ィエD1 channel / diabetes melliitus / neuropathy / hyperalgesia / 膜電位固定
Research Abstract

To Clarify the mechanism of hyperalgesia in diabetic neuropathy, we investigated the effects of streptozocin-induced hyperglycemia on tetrodotoxin-resistant NaィイD1+ィエD1 channel activity of dorsal root ganglion neurons. Experiments were performed on enzymatically isolated neurons of dorsal root ganglia dissected from streptozocin-induced diabetic and their age-matched control rats. Membrane currents were recorded using the whole-cell patch clamp technique. Mean current density of tetrodotoxin-resistant NaィイD1+ィエD1 channels was significantly larger in neurons prepared from diabetic rats than in their control neurons. Tetrodotoxin-resistant NaィイD1+ィエD1channels were activated at more negative potentials in diabetic than in their control neurons. Curves representing the steady-state inactivation and the peak NaィイD1+ィエD1 conductance as function of membrane potential have shifted to the negative side. The changes in gating property of the NaィイD1+ィエD1 channel were observed in 6 week after the injection of streptozocin, and still after 8 months diabetic rats, indicating that tetrodotoxin-resistant NaィイD1+ィエD1 channel abnormality starts to develop early and persists during the whole period of diabetes. These results suggest that neurons participating in nociception are highly excitable in diabetic animals. The present results may provide an important clue to the elucidation of hyperalgesia in diabetes.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report

Research Products

(8 results)

All Other

All Publications (8 results)

  • [Publications] Hirade M, et al.: "Tetrodotoxin-resistant sodium channels of dorsal root ganglion neuron are readily in diabetic rats"Neuroscience. 90. 933-939 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirade M, et al.: "PKC-mediated regulation of Na currents is impaired in dorsal root ganglion neurons of diabetic rats"J peripher Nerv Syst. 2. 271 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirade M, et al.: "Tetrodotoxin-resistant sodium channels of dorsal root ganglion neuron are readily activated in diabetic rats"Neuroscience. 90. 933-939 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirade M, et al.: "PKC-mediated regulation of Na currents is impaired indorsal root ganglion neurons of diabetic rats"J. Peripher Nerv Syst. 2 : 271. 271 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirade M et al.: "Tetrodotoxin-resistant sodium channels of dorsal root ganglion neuron are readily activated in diabetic rats"Neuroscience. 90. 933-939 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirade M et al.: "PKC-mediated regulation of Na currents is impaired in dorsal root ganglion neurons of diabetic rats"J Peripher Nerv Syst. 2. 271 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirade M,et al.: "Tetrodotoxin- resistant sodium channels of dorsal root ganglion neuron are readily activated in diabetic rats." Neuroscience. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirade M et al.: "PKC-mediated regulation of Na currents is impaired in dorsal root ganglion neurons of diabetic rats." J.Peripher New Syst. 2. 271 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-03-31   Modified: 2016-04-21  

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