Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy
- PMID: 16921370
- DOI: 10.1038/nn1754
Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy
Erratum in
- 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.
Comment in
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A possible explanation for the paradox of hyperexcitability and epilepsy in "loss of function" voltage-gated sodium channel mutations.Epilepsy Curr. 2007 Mar-Apr;7(2):54-55. doi: 10.1111/j.1535-7511.2007.00168.x. Epilepsy Curr. 2007. PMID: 17505554 Free PMC article. No abstract available.
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