Sodium channel mutations in epilepsy and other neurological disorders
Miriam H. Meisler, Jennifer A. Kearney
Miriam H. Meisler, Jennifer A. Kearney
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2010-2017. https://doi.org/10.1172/JCI25466.
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Sodium channel mutations in epilepsy and other neurological disorders

Abstract

Since the first mutations of the neuronal sodium channel SCN1A were identified 5 years ago, more than 150 mutations have been described in patients with epilepsy. Many are sporadic mutations and cause loss of function, which demonstrates haploinsufficiency of SCN1A. Mutations resulting in persistent sodium current are also common. Coding variants of SCN2A, SCN8A, and SCN9A have also been identified in patients with seizures, ataxia, and sensitivity to pain, respectively. The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological disease and may contribute to psychiatric disorders as well.

Authors

Miriam H. Meisler, Jennifer A. Kearney

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Figure 3

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The effects of GEFS+ mutations on SCN1A channel properties have been stu...
The effects of GEFS+ mutations on SCN1A channel properties have been studied in the Xenopus oocyte system and in transfected mammalian cells. (A) Whole-cell recordings from HEK tsA201 cells transfected with the indicated mutant SCN1A cDNAs demonstrate increased persistent current from the mutant channels (39). (B) Mean normalized amplitudes of sodium currents elicited by 80-Hz pulse trains in HEK cells expressing SCN2A cDNA containing the GEFS+ mutation D188V demonstrate reduced cumulative inactivation of the mutant channel during high-frequency trains of channel activation (40). (C) Voltage-dependent gating of SCN1A cDNA constructs in Xenopus oocytes expressed in the absence (left) or presence (right) of the β1 cDNA (85). See text for discussion.