1999 Fiscal Year Final Research Report Summary
Cross-link of signal transduction and channel function diabetic neuropathy
| Project/Area Number |
09670652
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
YASUDA Hitoshi Shiga University of Medical Science, Third Department of Medicine, Assistant Professor, 医学部, 講師 (80135467)
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| 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)
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| Project Period (FY) |
1997 – 1999
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| Keywords | dorsal root ganglion / tetrodotoxin-resistant / NaィイD1+ィエD1 channel / diabetes melliitus / neuropathy / hyperalgesia / 膜電位固定 |
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| 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.
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