Disease relevance of SCN11A

• Both channels are sensory neuron specific with SNS2 restricted entirely to those small dorsal root ganglion (DRG) cells with unmyelinated axons (C-fibers) [1].
• Injured nerves from human neonates showed similar results for both channels, but neonate neuromas lacked the SNS2/NaN 180 kDa molecular form, which was strongly present in adult neuromas [2].
• Selective SNS/PN3- and NaN/SNS2-blocking agents may provide new therapy for back pain and sciatica [3].

Psychiatry related information on SCN11A

• In this chapter, evidence of an important role for post-translational regulation of Nav1.9 in setting pain thresholds is presented [4].

High impact information on SCN11A

• NaN/Nav1.9 carried LVA currents into type-I (CI) and type-II (CII) small nociceptors and medium-Adelta-like nociceptive cells but not in low-threshold mechanoreceptors, including putative Down-hair (D-hair) and Aalpha/beta cells [5].
• Low voltage-activated (LVA) T-type Ca(2+) (I(Ca)T) and NaN/Nav1.9 currents regulate DRG neurons by setting the threshold for the action potential [5].
• NaN/Nav1.9 was inhibited by inorganic I(Ca) blockers as follows (IC(50), muM): La(3+) (46) > Cd(2+) (233) > Ni(2+) (892) and by mibefradil, a non-dihydropyridine I(Ca)T antagonist [5].
• SNS and SNS2 are found both in NGF-responsive and GDNF-responsive C-fibers and many of these cells also express the capsaicin receptor VR1 [1].
• About half of C-fiber DRG neurons express either SNS or SNS2, and in most, the channels are colocalized [1].

Biological context of SCN11A

• The human gene, SCN11A, was mapped to the conserved linkage group on chromosome 3p21-p24, close to human SCN5A and SCN10A [6].
• The deduced amino acid sequence of SCN12A shows 37-73% similarity with various other mammalian sodium channels [7].
• The longest open reading frame of SCN12A encodes 1791 amino acid residues [7].
• Two alternative splicing variants for SCN12A have been identified [7].
• SCN12A maps to human chromosome 3p23-p21 [7].

Anatomical context of SCN11A

• RESULTS: Expression of eight different VGSCalpha genes (SCN1A-4A, SCN7A-9A, and SCN11A) was determined in the PC cell lines [8].
• Although expression level could not be determined, SCN12A is also expressed in dorsal root ganglia (DRG) [7].
• Both neurons and glial cells express SCN12A [7].
• 3. These results suggest that SCN12A is a tetrodotoxin-resistant (TTX-R) sodium channel expressed in the central nervous system and nonneural tissues [7].
• The differential distribution of two tetrodotoxin resistant (TTXr) voltage-gated sodium channels SNS (PN3) and SNS2 (NaN) in rat primary sensory neurons has been investigated [1].

Other interactions of SCN11A

• Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states [9].
• Remarkably, two voltage-gated sodium channel genes (Nav1.8 and Nav1.9) are expressed selectively in damage-sensing peripheral neurons, while a third channel (Nav1.7) is found predominantly in sensory and sympathetic neurons [10].

Analytical, diagnostic and therapeutic context of SCN11A

• Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca2+ Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons [5].

References