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Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype

Nature Neuroscience volume 10, pages 405–409 (2007)Cite this article

An Erratum to this article was published on 01 June 2007

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Abstract

What is the relationship between sodium channel function, neuronal function and clinical status in channelopathies of the nervous system? Given the central role of sodium channels in the generation of neuronal activity, channelopathies involving sodium channels might be expected to cause either enhanced sodium channel function and neuronal hyperexcitability associated with positive clinical manifestations such as seizures, or attenuated channel function and neuronal hypoexcitability associated with negative clinical manifestations such as paralysis. In this article, I review observations showing that changes in neuronal function and clinical status associated with channelopathies are not necessarily predictable solely from the altered physiological properties of the mutated channel itself. I discuss evidence showing that cell background acts as a filter that can strongly influence the effects of ion channel mutations.

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Figure 1: Relationships between sodium channel function, neuronal function and clinical status.
Figure 2: The L858H erythromelalgia mutation depolarizes DRG neurons and renders them hyperexcitable.
Figure 3: The L858H erythromelalgia mutation depolarizes sympathetic ganglion neurons and renders them hypoexcitable.
Figure 4: An example of the importance of cell background: the selective presence of Nav1.8 channels in DRG neurons, but not sympathetic ganglion neurons, accounts for the opposing actions of Nav1.7 mutant channels on excitability in the two cell types.

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  1. The author is in the Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, USA, and at the Neuro Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut 06516, USA. stephen.waxman@yale.edu.,

    Stephen G Waxman

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Waxman, S. Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype. Nat Neurosci 10, 405–409 (2007). https://doi.org/10.1038/nn1857

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