Disease relevance of Scn7a

• A cDNA clone isolated from a rat dorsal root ganglion library encodes a 195 kDa voltage-gated sodium channel-like protein (SCL-11) with homology to the mouse (87%) and human (72%) atypical Na+ channels and rat partial clone NaG (98%) [1].
• Using in vivo footprint experiments, we demonstrate that several sites of the Na-G proximal promoter region are bound specifically by nuclear proteins in dorsal root ganglion neurons, as compared with nonexpressing hepatoma cells [2].

High impact information on Scn7a

• By Northern blot, RNase protection, and in situ hybridization assays, we demonstrate that, in addition to brain astroglia, the Na-G mRNA is expressed in cultures of Schwann cells derived from dorsal root ganglia or from sciatic nerve [3].
• The amino acid sequence deduced from this cDNA indicates that the Na-G represents a separate molecular class within the mammalian Na-channel multigene family [3].
• In vivo, the Na-G mRNA is detected not only in brain, dorsal root ganglia, and sciatic nerve, but also in tissues outside the nervous system including cardiac and skeletal muscle and lung [3].
• The Na-G ion channel, previously cloned from a rat astroglia cDNA library, belongs to a new family of ion channels, related to but distinct from the predominant brain and muscle fast voltage-gated Na(+) channels [4].
• Finally, Na-G/reporter constructs are shown to sustain a low but reproducible transcriptional response to cAMP, accounting in part for the elevation in mRNA level elicited by cAMP in Schwann cells and its reduction in astrocytes [4].

Biological context of Scn7a

• In vivo footprinting experiments revealed binding of glial-specific nuclear factors to several sites of the Na-G promoter region [4].
• By transient transfection of Na-G/reporter constructs into cultured cells, we show that a short genomic region, encompassing the first exon and 375 bp upstream, bears a high glial-specific transcriptional activity while part of the first intron behaves as a negative regulatory element [4].
• In the present report, we show that Na-G messenger RNA level in astrocyte and Schwann cell cultures is modulated in a cell-specific manner by several growth factors, hormones, and intracellular second messengers pathways [4].
• The expression of rat brain sodium channel alpha-subunit mRNAs I, II and III and a putative glial cell-specific sodium channel (NaG) mRNA was examined in cultured astrocytes from P-0 rat spinal cord by RNA blot hybridization and by non-isotope in situ hybridization cytochemistry utilizing two independent sets of isoform-specific RNA probes [5].

Anatomical context of Scn7a

• NaG, a member of subfamily 2, was originally characterized as a "glial" sodium channel, and is expressed at high levels in Schwann cells in vivo [6].
• NaG: a sodium channel-like mRNA shared by Schwann cells and other neural crest derivatives [6].
• NaG thus appears to represent a transcript encoding a sodium channel or sodium channel-like protein that is uniquely expressed by both Schwann cells and afferent neurons of neural crest origin [6].
• Na-G is a putative sodium (or cationic) channel expressed in neurons and glia of the PNS, in restricted neuronal subpopulations of the brain, and in several tissues outside the nervous system, like lung and adrenal medulla [2].
• NaG was not observed in sensory neurons (retina, vestibular ganglion, spiral ganglion, olfactory epithelium) that are not of neural crest origin [6].

Analytical, diagnostic and therapeutic context of Scn7a

• In the present study, we used non-isotopic in situ hybridization with a riboprobe for NaG, in conjunction with RT-PCR, to determine whether NaG is expressed in tissues related to the DRG either by neural crest origin or sensory function [6].

References