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

Kv1.1和Kv1.2是shaker样基因亚家族中两个最密切相关的成员，它们编码电压门控钾（K^+）通道的成孔亚基。为了阐明这些蛋白在初级感觉传入中的生理作用，我们使用特异性抗体进行了免疫组织化学分析。背根和三叉神经节免疫过氧化物酶染色显示，中大型神经元中Kv1.1和Kv1.2的免疫反应性较强。在双免疫荧光实验中，在RT97（神经丝）阳性的大神经元中最常观察到这些亚基强阳性的细胞；但很少发生在外周蛋白或ib4阳性的小神经元中。在脊髓背角，aanti - kv1.1和anti-Kv1.2抗体在更深的III-IV层都有严重的染色。在电镜水平上，这些蛋白的IRs优先定位于有髓鞘的大直径轴突。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^+通道可能在传导皮肤和肌肉的机械感觉和本体感觉中起重要作用。可以想象，损伤后这些通道表达的减少可能会导致神经元的过度兴奋性，从而导致代偿性亢进或异常性疼痛。

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.