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Scn8a encodes the alpha subunit of the type VIII voltage-gated sodium channel. These channels, composed of one alpha and one or two beta subunits, mediate changes in cell permeability to sodium ions that are essential for the generation of action potentials. The alpha subunit alone has been shown to generate a functional channel in vitro, but it's kinetic properties are modulated by beta subunits. The type VIII channel is believed to be responsible for distinct sodium conductances underlying repetitive firing of action potentials in Purkinje neurons. Scn8a channels are tetrodotoxin sensitive. At least two alternatively spliced mRNA variants have been reported. These variants result from two alternatively spliced exons, 18N and 18A, that encode transmembrane segments S3 and S4 in domain III. Mutations in mouse Scn8a have been shown to result in neurological disorders, including paralysis, ataxia, and dystonia. Absence of Scn8a sodium channels is associated with the phenotype "motor end plate disease," which is characterized by a progressive neuromuscular failure and is fatal by 3-4 postnatal weeks.
Gene Name: | sodium channel, voltage gated, type VIII, alpha subunit |
Family/Subfamily: | Ion Channel , Sodium channel - voltage-gated |
Synonyms: | SCN8A, CERIII, MED, PN4, Na6, NaCh6, CIAT, Dmu, EIEE13, Motor endplate disease, Nav1.6, PN4a |
Target Sequences: | NM_014191 NP_055006.1 Q9UQD0 |
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