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

SG Waxman - Nature neuroscience, 2007 - nature.com
Nature neuroscience, 2007nature.com
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 …
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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