Cross-link of signal transduction and channel function diabetic neuropathy

信号转导与通道功能的交联糖尿病神经病变

• 批准号: 09670652
• 负责人: YASUDA Hitoshi
• 金额: $ 2.05万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670652/
• 关键词: dorsal root ganglion; tetrodotoxin-resistant; NaィイD1+ィエD1 channel; diabetes melliitus; neuropathy; hyperalgesia; 膜電位固定

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.

为阐明痛觉过敏在糖尿病神经病变中的作用机制，我们观察了链脲佐菌素诱导的高血糖对背根神经节神经元河豚毒素抗性NaィイD 1+ィエD 1通道活性的影响。对链佐菌素诱导的糖尿病大鼠及其年龄匹配的对照组大鼠背根神经节进行了酶法分离的神经元实验。采用全细胞膜片钳技术记录膜电流。糖尿病大鼠神经元对河豚毒素抗性的NaィイD1+ィエD1通道的平均电流密度明显大于其对照神经元。糖尿病大鼠对河豚毒素抗性的Na-ィイ-D_1+ィエ-D_1通道在更大的负电位下被激活。稳态失活曲线和峰值NaィイD_1+ィエD_1电导随膜电位的变化曲线向负侧移动。糖尿病大鼠注射链脲佐菌素后6周即可观察到NaィイD 1+ィエD 1通道门控特性的变化，8个月后仍有变化，提示河豚毒素抗性NaィイD 1+ィエD 1通道异常开始出现较早，并持续整个糖尿病病程。这些结果表明，在糖尿病动物中，参与伤害感受的神经元是高度兴奋的。本研究结果可能为阐明糖尿病痛觉过敏提供重要线索。

项目成果

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)

Hirade M 等人：“PKC 介导的 Na 电流调节会损害糖尿病大鼠的背根神经节神经元”J.

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)

Hirade M 等人：“糖尿病大鼠的背根神经节神经元中 PKC 介导的 Na 电流调节受到损害。”

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

Hirade M 等人：“糖尿病大鼠的背根神经节神经元很容易出现河豚毒素抗性钠通道”神经科学。

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

Hirade M 等人：“糖尿病大鼠的背根神经节神经元的河豚毒素抗性钠通道很容易被激活”神经科学。

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

Hirade M 等人：“糖尿病大鼠的背根神经节神经元的河豚毒素抗性钠通道很容易被激活”神经科学。