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Voltage-gated Na+ channels: multiplicity of expression, plasticity, functional implications and pathophysiological aspects

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Abstract

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, fibroblasts 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 α-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 trafficking of VGSC protein.

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Acknowledgements

We gratefully acknowledge the support of Cancer Research UK (CRUK), the Medical Research Council (MRC), The Wellcome Trust, and the Pro Cancer Research Fund (PCRF).

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  1. Neuroscience Solutions to Cancer Research Group, Department of Biological Sciences, Imperial College London, South Kensington Campus, Imperial College Road, London , SW7 2AZ, UK

    J. K. J. Diss, S. P. Fraser & M. B. A. Djamgoz

  2. Medical Molecular Biology Unit, Institute of Child Health, University College London, London, WC1N 1EH, UK

    J. K. J. Diss

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  1. J. K. J. Diss
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Correspondence to S. P. Fraser.

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Presented at the Biophysical Society Meeting on “Ion channels – from biophysics to disorders” held in May 2003, Rennes, France

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Diss, J.K.J., Fraser, S.P. & Djamgoz, M.B.A. Voltage-gated Na+ channels: multiplicity of expression, plasticity, functional implications and pathophysiological aspects. Eur Biophys J 33, 180–193 (2004). https://doi.org/10.1007/s00249-004-0389-0

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