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http://purl.uniprot.org/citations/17928448http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17928448http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17928448http://www.w3.org/2000/01/rdf-schema#comment"Loss-of-function mutations of Na(V)1.1 channels cause severe myoclonic epilepsy in infancy (SMEI), which is accompanied by severe ataxia that contributes substantially to functional impairment and premature deaths. Mutant mice lacking Na(V)1.1 channels provide a genetic model for SMEI, exhibiting severe seizures and premature death on postnatal day 15. Behavioral assessment indicated severe motor deficits in mutant mice, including irregularity of stride length during locomotion, impaired motor reflexes in grasping, and mild tremor in limbs when immobile, consistent with cerebellar dysfunction. Immunohistochemical studies showed that Na(V)1.1 and Na(V)1.6 channels are the primary sodium channel isoforms expressed in cerebellar Purkinje neurons. The amplitudes of whole-cell peak, persistent, and resurgent sodium currents in Purkinje neurons were reduced by 58-69%, without detectable changes in the kinetics or voltage dependence of channel activation or inactivation. Nonlinear loss of sodium current in Purkinje neurons from heterozygous and homozygous mutant animals suggested partial compensatory upregulation of Na(V)1.6 channel activity. Current-clamp recordings revealed that the firing rates of Purkinje neurons from mutant mice were substantially reduced, with no effect on threshold for action potential generation. Our results show that Na(V)1.1 channels play a crucial role in the excitability of cerebellar Purkinje neurons, with major contributions to peak, persistent, and resurgent forms of sodium current and to sustained action potential firing. Loss of these channels in Purkinje neurons of mutant mice and SMEI patients may be sufficient to cause their ataxia and related functional deficits."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.org/dc/terms/identifier"doi:10.1523/jneurosci.2162-07.2007"xsd:string
http://purl.uniprot.org/citations/17928448http://purl.org/dc/terms/identifier"doi:10.1523/jneurosci.2162-07.2007"xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Catterall W.A."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Catterall W.A."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Scheuer T."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Scheuer T."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Westenbroek R.E."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Westenbroek R.E."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Yu F.H."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Yu F.H."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Kalume F."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/author"Kalume F."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/date"2007"xsd:gYear
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/name"J. Neurosci."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/name"J. Neurosci."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/pages"11065-11074"xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/pages"11065-11074"xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/title"Reduced sodium current in Purkinje neurons from Nav1.1 mutant mice: implications for ataxia in severe myoclonic epilepsy in infancy."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/title"Reduced sodium current in Purkinje neurons from Nav1.1 mutant mice: implications for ataxia in severe myoclonic epilepsy in infancy."xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/volume"27"xsd:string
http://purl.uniprot.org/citations/17928448http://purl.uniprot.org/core/volume"27"xsd:string
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