Voltage-gated Na+ channels:: multiplicity of expression, plasticity, functional implications and pathophysiological aspects
Voltage-gated Na+ channels:: multiplicity of expression, plasticity, functional implications and pathophysiological aspects
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DOI：
10.1007/s00249-004-0389-0
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发表时间：
2004-05-01
影响因子：
2
通讯作者：
Djamgoz, MBA
中科院分区：
文献类型：
--
作者：
Diss, JKJ;Fraser, SP;Djamgoz, MBA
众所周知，电压门控Na+通道（VGSC）介导神经和肌肉中的再生细胞膜去极化和电信号传导。然而，VGSC也可以在传统的“非兴奋性”细胞类型中表达，包括淋巴细胞、神经胶质细胞、.成纤维细胞和上皮来源的转移性癌细胞。VGSC表达的多样性和调节比最初明显的要复杂得多。至少有10种不同的基因编码VGSC的α亚基。由于VGSC可导致一系列人类疾病，因此重要的是要了解VGSC功能的控制和后果以及这些方面在病理生理条件下如何改变。这种机制可以在转录、翻译前或翻译后水平上。本文回顾了最近的文献，有助于我们了解不同的VGSC亚型如何在不同的细胞类型中产生其独特的生理特征。我们还强调了新兴的感兴趣的领域，特别是，发现单个VGSC亚型在单细胞内的多种表达，产生选择性剪接变体和日益复杂的可塑性机制，通过这些机制，可以巧妙地控制单个VGSC亚型，包括VGSC蛋白的细胞内跟踪。
Voltage- gated Na+ channels ( VGSCs) are well known for mediating regenerative cell membrane depolarization and conduction of electrical signalling in nerves and muscles. However, VGSCs may also be expressed in traditionally `` non- excitable'' cell types, including lymphocytes, glia,. broblasts and metastatic cancer cells of epithelial origin. Both the diversity and modulation of VGSC expression are far more complex than was initially apparent. There are at least 10 different genes that encode the alpha- subunits of VGSCs. Since VGSCs can contribute to a range of human disease conditions, it is important to understand both the control and consequences of VGSC functioning and how these aspects may be altered under pathophysiological conditions. Such mechanisms can be at the transcriptional, pre- translational or post- translational levels. This article reviews recent literature that has contributed to our understanding of how individual VGSC subtypes can generate their unique physiological signatures within different cell types. We also highlight emerging areas of interest, in particular, the finding of multiple expression of individual VGSC subtypes within single cells, the generation of alternative splice variants and the increasingly complex set of mechanisms of plasticity through which individual VGSC subtypes may be subtly controlled, including intracellular tracking of VGSC protein.