Molecular mechanism of neuropathic pain aberrant expression of voltage-gated sodium and potassium channels

电压门控钠钾通道异常表达神经病理性疼痛的分子机制

• 批准号: 11680753
• 负责人: YOKOYAMA Shigeru
• 金额: $ 2.18万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680753/
• 关键词: voltage-gated potassium channel; Kv1.1; Kv1.2; 膜電位依存性K+チャネル; 膜電位依存性^+チャネル; 膜電位依存性K^+チャネル

Kv1.1 and Kv1.2, two most closely related members of the Shaker-like gene subfamily, encode pore-forming subuaits of voltage-gated potassium (K^+) channels. To clarify physiological roles of these proteins in primary sensory afferentiation, we have performed inimunohistochemical analysis using specific antidodies. Immunoperoxidase staining of dorsal root and trigeminal ganglia revealed that strong immunoreactivity (IR) for Kv1.1 and Kv1.2 was predominant in medium- and large-sized neurons. In double-immunofluorescence experiments, the cells strongly positive for these subunits were most frequently observed in RT97 (neurofilament)-positive large neurons; but rarely in peripherin- or IB4-positive small neurons. In the spinal dorsal horn, both the aati-Kv1.1 and anti-Kv1.2 antibodies heavily staiaed the deeper laminae III-IV. At the electron microscopic level, IRs for these proteins were preferentially localized in myelinated axons with large diameter. These results suggest that voltage-gated K^+ channels composed of Kv 1.1 and/or Kv 1.2 subunits may play important roles in conducting mechanoceptive and proprioceptiye sensation from skin and muscles. Conceivably, decreased expression of these channels after injury might cause hypereexcitability of neurons, thereby leading to hyperalgegia or allodyaia.

KV1.1和KV1.2，这是振动振荡器的两个最紧密相关的成员，编码了电压门控钾（K^+）通道的孔形成子图。为了阐明这些蛋白质在主要感觉传统中的生理作用，我们使用特定的抗体进行了非节向组织化学分析。背根和三叉神经节的免疫过氧化物酶染色表明，KV1.1和KV1.2的强免疫反应性（IR）在中和大尺寸神经元中主要是主导。在双免疫荧光实验中，这些亚基的细胞在RT97（神经丝）阳性大神经元中最常观察到这些亚基的阳性。但是很少在外周或IB4阳性小神经元中。在脊柱背角中，AATI-KV1.1和抗Kv1.2抗体都严重地固定了更深的Laminae IIII-II-II-II-II-II-IV。在电子显微镜水平上，这些蛋白质的IRS优先定位在直径较大的髓鞘轴突中。这些结果表明，由KV 1.1和/或kV 1.2亚基组成的电压门控k^+通道可能在从皮肤和肌肉中传导机械感受和前置感受中起着重要作用。可以想象，受伤后这些通道的表达降低可能会导致神经元过度兴奋性，从而导致超级高菌或同差。

项目成果

横山茂: "細胞膜受容体の構造分類と機能特性"日本臨床. 60. 218-220 (2002)

Shigeru Yokoyama：“细胞膜受体的结构分类和功能特征”日本临床研究 60. 218-220 (2002)。

Yokoyama, S., Takeda, H., and Higashida, H.: "Expression of Kvl.2 potassium channels in rat sensory ganglia: an immuaohistochemical study."Ann. NY. Acad. Sci.. 868. 454-457 (1999)

Yokoyama, S.、Takeda, H. 和 Higashida, H.：“大鼠感觉神经节中 Kvl.2 钾通道的表达：一项免疫组织化学研究。”Ann。

Macica, C. M., von Hehn, C. A. A., Yang-Wang, L., Ho, C. S., Yokoyama, S., Joho, R. H., and Kaczmarek, L. K.: "Modulation of the Kv3.1b potassium channel isoform adjusts the fidelity of the firing pattern of auditory neurons."J. Neurosci.. 23. 1133-1141 (

Macica, C. M.、von Hehn, C. A. A.、Yang-Wang, L.、Ho, C. S.、Yokoyama, S.、Joho, R. H. 和 Kaczmarek, L. K.：“Kv3.1b 钾通道亚型的调节可调节放电的保真度

Yokoyama, S.et al.: "Expression of Kv1.2 potassium channels in rat sensory ganglia : an immunohistochemical study"Ann.NY Acad.Sci.. 868. 454-457 (1999)

Yokoyama, S.et al.：“大鼠感觉神经节中 Kv1.2 钾通道的表达：免疫组织化学研究”Ann.NY Acad.Sci.. 868. 454-457 (1999)

Macica, C.M.et al.: "Modulation of the Kv3.1b potassium channel isoform adjusts the fidelity of the firing pattern of auditory neurons"J.Neurosci. 23. 1133-1141 (2003)

Macica, C.M. 等人：“Kv3.1b 钾通道亚型的调节可调整听觉神经元放电模式的保真度”J. Neurosci。