Genomes and Genes
Gene Symbol: Scn8a
Description: sodium voltage-gated channel alpha subunit 8
Alias: sodium channel protein type 8 subunit alpha, Na+ channel, PN4, naCh6, peripheral nerve protein type 4, sodium channel 6, sodium channel protein type VIII subunit alpha, sodium channel, voltage gated, type VIII, alpha subunit, sodium channel, voltage-gated, type 8, alpha polypeptide, sodium channel, voltage-gated, type 8, alpha subunit, sodium channel, voltage-gated, type VIII, alpha polypeptide, voltage-gated sodium channel subunit alpha Nav1.6
- Lorincz A, Nusser Z. Molecular identity of dendritic voltage-gated sodium channels. Science. 2010;328:906-9 pubmed publisher..Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability. ..
- Du Y, Huang X, Wang T, Han K, Zhang J, Xi Y, et al. Downregulation of neuronal sodium channel subunits Nav1.1 and Nav1.6 in the sinoatrial node from volume-overloaded heart failure rat. Pflugers Arch. 2007;454:451-9 pubmed..1 and Nav1.6 expression contributes to HF-induced SAN dysfunction. These findings provide additional information about molecular basis of disease-related impairment of SAN function. ..
- Komada M, Soriano P. [Beta]IV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. J Cell Biol. 2002;156:337-48 pubmed..These results indicate that betaIV-spectrin and ankyrin-G mutually stabilize the membrane protein cluster and the linked membrane cytoskeleton at AIS and NR. ..
- Malhotra J, Thyagarajan V, Chen C, Isom L. Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J Biol Chem. 2004;279:40748-54 pubmed..5 and pYbeta1 and that these complexes are in close association with both N-cadherin and connexin-43. beta1 phosphorylation appears to regulate its localization to differential subcellular domains. ..
- Akin E, Sole L, Johnson B, Beheiry M, Masson J, Krapf D, et al. Single-Molecule Imaging of Nav1.6 on the Surface of Hippocampal Neurons Reveals Somatic Nanoclusters. Biophys J. 2016;111:1235-1247 pubmed publisher..6 was observed to be transiently trapped in the nanoclusters. Somatic Nav1.6 nanoclusters represent a new, to our knowledge, type of Nav channel localization, and are hypothesized to be sites of localized channel regulation. ..
- Ptak K, Zummo G, Alheid G, Tkatch T, Surmeier D, McCrimmon D. Sodium currents in medullary neurons isolated from the pre-Bötzinger complex region. J Neurosci. 2005;25:5159-70 pubmed..In the rostral ventral respiratory group (immediately caudal to preBötC), I(NaP) was also detected, but peak conductance, current density, and input resistance were smaller than in preBötC region cells. ..
- Blanchard M, Willemsen M, Walker J, Dib Hajj S, Waxman S, Jongmans M, et al. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. J Med Genet. 2015;52:330-7 pubmed publisherMutations of SCN8A encoding the neuronal voltage-gated sodium channel NaV1.6 are associated with early-infantile epileptic encephalopathy type 13 (EIEE13) and intellectual disability...
- Buchner D, Seburn K, Frankel W, Meisler M. Three ENU-induced neurological mutations in the pore loop of sodium channel Scn8a (Na(v)1.6) and a genetically linked retinal mutation, rd13. Mamm Genome. 2004;15:344-51 pubmed..Failure to complement a mutant allele of a positional candidate gene, Scn8a, demonstrated that the mutations are new alleles of Scn8a...
- Koay G, Heffner R, Heffner H. Behavioral audiograms of homozygous med(J) mutant mice with sodium channel deficiency and unaffected controls. Hear Res. 2002;171:111-118 pubmed..The med(J) mutation results in greatly reduced levels of Scn8a voltage-gated sodium channels, which causes abnormal conduction of action potentials throughout the nervous system ..
- Schafer D, Custer A, Shrager P, Rasband M. Early events in node of Ranvier formation during myelination and remyelination in the PNS. Neuron Glia Biol. 2006;2:69-79 pubmed..We suggest there is heterogeneity in the events leading to Nav channel clustering, indicating that multiple mechanisms might contribute to node of Ranvier formation in the PNS. ..
- Chen Z, Chen S, Chen L, Zhou J, Dai Q, Yang L, et al. Long-term increasing co-localization of SCN8A and ankyrin-G in rat hippocampal cornu ammonis 1 after pilocarpine induced status epilepticus. Brain Res. 2009;1270:112-20 pubmed publisher..Here we investigated the alterations of the two alpha-subunits SCN8A and SCN1A and their adapter ankyrin-G in the hippocampal cornu ammonis 1 (CA1) of rats after pilocarpine induced ..
- Laezza F, Lampert A, Kozel M, Gerber B, Rush A, Nerbonne J, et al. FGF14 N-terminal splice variants differentially modulate Nav1.2 and Nav1.6-encoded sodium channels. Mol Cell Neurosci. 2009;42:90-101 pubmed publisher..Thus, the FGF14 N-terminus is required for targeting and functional regulation of Nav channels, suggesting an important function for FGF14 alternative splicing in regulating neuronal excitability. ..
- Sills M, Xu Y, Baracchini E, Goodman R, Cooperman S, Mandel G, et al. Expression of diverse Na+ channel messenger RNAs in rat myocardium. Evidence for a cardiac-specific Na+ channel. J Clin Invest. 1989;84:331-6 pubmed
- Akin E, SolÃ© L, Dib Hajj S, Waxman S, Tamkun M. Preferential targeting of Nav1.6 voltage-gated Na+ Channels to the axon initial segment during development. PLoS ONE. 2015;10:e0124397 pubmed publisher..6 insertion into the AIS plasma membrane. In contrast, ankyrinG-binding alone does not confer the preferential delivery of proteins to the AIS. ..
- Xi Y, Wu G, Yang L, Han K, Du Y, Wang T, et al. Increased late sodium currents are related to transcription of neuronal isoforms in a pressure-overload model. Eur J Heart Fail. 2009;11:749-57 pubmed publisher..26.15 +/- 5.17 pA/pF, P < 0.01). Correspondingly, the relative mRNA levels of the neuronal isoforms SCN1a and SCN8a increased 2.5- and 2...
- Kalume F, Yu F, Westenbroek R, Scheuer T, Catterall W. Reduced sodium current in Purkinje neurons from Nav1.1 mutant mice: implications for ataxia in severe myoclonic epilepsy in infancy. J Neurosci. 2007;27:11065-74 pubmed..Loss of these channels in Purkinje neurons of mutant mice and SMEI patients may be sufficient to cause their ataxia and related functional deficits. ..
- Lopez Santiago L, Meadows L, Ernst S, Chen C, Malhotra J, McEwen D, et al. Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. J Mol Cell Cardiol. 2007;43:636-47 pubmed..Together, these results suggest that beta1 is critical for normal cardiac excitability and loss of beta1 may be associated with a long QT phenotype. ..
- Wittmack E, Rush A, Craner M, Goldfarb M, Waxman S, Dib Hajj S. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci. 2004;24:6765-75 pubmed..The preferential expression of FHF2B in sensory neurons may provide a basis for physiological differences in sodium currents that have been reported at the nodes of Ranvier in sensory versus motor axons. ..
- Buchner D, Trudeau M, Meisler M. SCNM1, a putative RNA splicing factor that modifies disease severity in mice. Science. 2003;301:967-9 pubmed..The primary mutation (medJ) changes a splice donor site of the sodium channel gene Scn8a (Nav1.6)...
- McCavera S, Soderlund D. Differential state-dependent modification of inactivation-deficient Nav1.6 sodium channels by the pyrethroid insecticides S-bioallethrin, tefluthrin and deltamethrin. Neurotoxicology. 2012;33:384-90 pubmed publisher..6Q3 channels in the open state and imply that the pyrethroid receptor of resting and open channels occupies different conformations that exhibit distinct structure-activity relationships. ..
- Dietrich P, McGivern J, Delgado S, Koch B, Eglen R, Hunter J, et al. Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia. J Neurochem. 1998;70:2262-72 pubmed..rat DRG we have cloned and functionally expressed a tetrodotoxin-sensitive sodium channel alpha subunit, NaCh6/Scn8a/rPN4, and a splice variant, rPN4a...
- Rush A, Craner M, Kageyama T, Dib Hajj S, Waxman S, Ranscht B. Contactin regulates the current density and axonal expression of tetrodotoxin-resistant but not tetrodotoxin-sensitive sodium channels in DRG neurons. Eur J Neurosci. 2005;22:39-49 pubmed
- Wittmack E, Rush A, Hudmon A, Waxman S, Dib Hajj S. Voltage-gated sodium channel Nav1.6 is modulated by p38 mitogen-activated protein kinase. J Neurosci. 2005;25:6621-30 pubmed..6 current density. This is the first demonstration of MAPK phosphorylation and modulation of a voltage-gated sodium channel, and this modulation may represent an additional role for MAPK in regulating the neuronal response to injury. ..
- Mechaly I, Scamps F, Chabbert C, Sans A, Valmier J. Molecular diversity of voltage-gated sodium channel alpha subunits expressed in neuronal and non-neuronal excitable cells. Neuroscience. 2005;130:389-96 pubmed..6 occurring at the exon 18 of the mouse orthologue SCN8A, we revealed that this subunit co-exist in the two cell types under different alternative spliced isoforms...
- Henry M, Freking A, Johnson L, Levinson S. Sodium channel Nav1.6 accumulates at the site of infraorbital nerve injury. BMC Neurosci. 2007;8:56 pubmed..The changes identified in this study suggest that the participation of Nav1.6 should be considered when examining changes in the excitability of myelinated axons in neuropathic pain models. ..
- Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, et al. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci. 2007;27:5903-14 pubmed..Our data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and, furthermore, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. ..