Sodium channel Nav1.6 is localized at nodes of Ranvier, dendrites, and synapses
Sodium channel Nav1.6 is localized at nodes of Ranvier, dendrites, and synapses
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DOI：
10.1073/pnas.090034797
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发表时间：
2000-05-09
影响因子：
11.1
通讯作者：
Levinson, SR
中科院分区：
文献类型：
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作者：
Caldwell, JH;Schaller, KL;Levinson, SR
电压门控钠通道通过在轴突和树突中产生动作电位，对神经系统中的电信号起着关键作用。在哺乳动物中，至少有10个基因编码钠通道，但区分这些异构体的具体生理作用尚不清楚。一种可能性是，每种异构体都在一组有限的细胞类型中表达，或者针对神经元或肌肉细胞的特定区域。利用亲和纯化的异构体特异性抗体，我们发现Na(V)1.6在周围神经系统感觉轴突和运动轴突的Ranvier结节和中枢神经系统的结节上高度集中。用Na(V)1.6免疫染色阴性的缺乏Na(V)1.6的小鼠突变株MED也证明了该抗体的特异性。标记的强度和其他异构体特异性抗体标记结节的失败都表明Na(V)1.6是这种结构中的主要通道类型。在中枢神经系统中，N(V)1.6定位于视网膜和小脑的无髓轴突，在皮质锥体细胞和小脑浦肯野细胞的树突中有较强的表达。超微结构研究表明，树突中的标记既存在于细胞内，也存在于树突轴膜上。值得注意的是，在皮质和小脑的突触前膜和突触后膜上都观察到了Na(V)1.6标记，因此，单一的钠通道亚型针对不同的神经元域，可以影响轴突传导和突触反应。
Voltage-gated sodium channels perform critical roles for electrical signaling in the nervous system by generating action potentials in axons and in dendrites. At least 10 genes encode sodium channels in mammals, but specific physiological roles that distinguish each of these isoforms are not known. One possibility is that each isoform is expressed in a restricted set of cell types or is targeted to a specific domain of a neuron or muscle cell. Using affinity-purified isoform-specific antibodies, we find that Na(v)1.6 is highly concentrated at nodes of Ranvier of both sensory and motor axons in the peripheral nervous system and at nodes in the central nervous system. The specificity of this antibody was also demonstrated with the Na(v)1.6-deficient mouse mutant strain med, whose nodes were negative for Na(v)1.6 immunostaining. Both the intensity of labeling and the failure of other isoform-specific antibodies to label nodes suggest that Na(v)1.6 is the predominant chan nel type in this structure. In the central nervous system, N(v)1.6 is localized in unmyelinated axons in the retina and cerebellum and is strongly expressed in dendrites of cortical pyramidal cells and cerebellar Purkinje cells. Ultrastructural studies indicate that labeling in dendrites is both intracellular and on dendritic shaft membranes. Remarkably, Na(v)1.6 labeling was observed at both presynaptic and postsynaptic membranes in the cortex and cerebellum Thus, a single sodium channel isoform is targeted to different neuronal domains and can influence both axonal conduction and synaptic responses.