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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Yu FH,Mantegazza M,Westenbroek RE,Robbins CA,Kalume F,Burton KA,Spain WJ,McKnight GS,Scheuer T,Catterall WAdoi
10.1038/nn1754subject
Has Abstractpub_date
2006-09-01 00:00:00pages
1142-9issue
9eissn
1097-6256issn
1546-1726pii
nn1754journal_volume
9pub_type
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