Disease relevance of Scn11a

• Glial-derived neurotrophic factor upregulates expression of functional SNS and NaN sodium channels and their currents in axotomized dorsal root ganglion neurons [1].

High impact information on Scn11a

• To further test this hypothesis, computer simulations were performed with a kinetic Na+ channel model that provided greater independent control of NaP relative to transient Na+ current (NaT) than that provided by riluzole administration [2].
• The Scn11a gene encoding this cDNA is organized into 24 exons [3].
• Unlike some alpha-subunits, Scn11a does not have an alternative exon 5 in domain I. Introns of the U2 and U12 spliceosome types are present at conserved positions relative to other members of this family [3].
• Previous studies have shown that sodium channel alpha-subunit NaN is preferentially expressed in small-diameter sensory neurons of dorsal root ganglia and trigeminal ganglia [3].
• Thus SNS and NaN channels appear to produce different currents in human DRG neurons [4].

Biological context of Scn11a

• We have cloned a tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel alpha subunit from a mouse cDNA library and designated it as NaT [5].
• NaT is detectable in mouse embryos 15 days postcoitus (p.c.), around the phase of organogenesis and gonadal differentiation [5].
• In this study, we asked whether glial-derived neurotrophic factor (GDNF), which has been shown to prevent some axotomy-induced changes such as the loss of somatostatin expression in DRG neurons, can ameliorate the axotomy-induced downregulation of SNS and NaN TTX-R sodium channels [1].
• The ability of the compounds to protect the AGS cells against the damage induced by sodium taurocholate (NaT), to stimulate the cellular reduced glutathione (GSH) and prostaglandin E(2) content, to enhance AGS and MRC-5 cell proliferation and to scavenge superoxide anion in vitro was studied [6].

Anatomical context of Scn11a

• Two tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels, SNS and NaN, are preferentially expressed in small dorsal root ganglia (DRG) and trigeminal ganglia neurons, most of which are nociceptive, of rat and mouse [4].
• We previously demonstrated that, after sciatic nerve transection, the levels of SNS and NaN sodium channel alpha-subunit transcripts and protein in small (18-30 micrometer diameter) DRG neurons are reduced, as are the amplitudes and densities of the slowly inactivating and persistent TTX-R currents produced by these two channels [1].

Associations of Scn11a with chemical compounds

• When NaP was sharply reduced without significantly altering NaT, the model reproduced the effects of riluzole administration, inducing failure of repetitive firing but allowing single spikes in response to sharp transients [2].

References