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Nat Neurosci. 2006 Sep;9(9):1142-9. Epub 2006 Aug 20.

Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy.

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1
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.

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  • Nat Neurosci. 2007 Jan;10(1):134.

Abstract

Voltage-gated sodium channels (Na(V)) are critical for initiation of action potentials. Heterozygous loss-of-function mutations in Na(V)1.1 channels cause severe myoclonic epilepsy in infancy (SMEI). Homozygous null Scn1a-/- mice developed ataxia and died on postnatal day (P) 15 but could be sustained to P17.5 with manual feeding. Heterozygous Scn1a+/- mice had spontaneous seizures and sporadic deaths beginning after P21, with a notable dependence on genetic background. Loss of Na(V)1.1 did not change voltage-dependent activation or inactivation of sodium channels in hippocampal neurons. The sodium current density was, however, substantially reduced in inhibitory interneurons of Scn1a+/- and Scn1a-/- mice but not in their excitatory pyramidal neurons. An immunocytochemical survey also showed a specific upregulation of Na(V)1.3 channels in a subset of hippocampal interneurons. Our results indicate that reduced sodium currents in GABAergic inhibitory interneurons in Scn1a+/- heterozygotes may cause the hyperexcitability that leads to epilepsy in patients with SMEI.

PMID:
16921370
DOI:
10.1038/nn1754
[Indexed for MEDLINE]
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