Disease relevance of Accn3

• ASIC3 knockouts do not develop mechanical hyperalgesia to repeated intramuscular acid injection when compared to wildtype littermates [1].
• Dorsal root ganglion neurons innervating muscle express ASIC3 and respond to acidic pH with fast, transient inward and sustained currents that resemble those of ASICs [1].
• A DRASIC knockout mouse model was tested for a hearing loss phenotype and was found to have normal hearing at 2 months of age but appeared to develop hearing loss early in life [2].

High impact information on Accn3

• The data suggest that DRASIC subunits participate in heteromultimeric channel complexes in sensory neurons [3].
• We localized one such channel, DRASIC, in several different specialized sensory nerve endings of skin, suggesting it might participate in mechanosensation and/or acid-evoked nociception [3].
• Loss of DRASIC increased the sensitivity of mechanoreceptors detecting light touch, but it reduced the sensitivity of a mechanoreceptor responding to noxious pinch and decreased the response of acid- and noxious heat-sensitive nociceptors [3].
• The biophysical properties of three degenerin/epithelial sodium (DEG/ENaC) channel subunits (BNC1, ASIC, and DRASIC), and their expression in DRG, suggest that they might underlie these H(+)-gated currents and function as sensory transducers [4].
• CONCLUSIONS: These data show that ASIC3 makes a critical positive contribution to mechanosensitivity in three out of four classes of visceral afferents [5].

Biological context of Accn3

• No differences in current amplitude or kinetics were found between ASIC2 and/or ASIC3 null mutants and controls [6].

Anatomical context of Accn3

• COS-7 cells heterologously expressing ASIC1 or ASIC3 showed similar effects [7].
• Characterisation of DRASIC in the mouse inner ear [2].
• Microarray analyses of the Soares NMIE library, consisting of 1536 cDNA clones isolated from the mouse inner ear, suggested that the expression of the mechanoreceptor DRASIC was enriched in the cochlea compared to other tissues [2].
• DRASIC protein was also detected in cells of the organ of Corti [2].
• Using in situ hybridisation and immunofluorescence, DRASIC expression was localised to the cells and neural fibre region of the spiral ganglion [2].

Associations of Accn3 with chemical compounds

• We found that neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe amide) and FMRFamide (Phe-Met-Arg-Phe amide) generated no current on their own but potentiated H+-gated currents from cultured sensory neurons and heterologously expressed ASIC and DRASIC channels [8].
• We show here that serine proteases modulate the function of ASIC1a and ASIC1b but not of ASIC2a and ASIC3 [9].

Other interactions of Accn3

• In particular ASIC3, the least abundant in the general population, is the most abundant ASIC transcript in colonic neurons [10].
• QPCR of whole thoracolumbar DRG revealed and abundance of ASIC2 > ASIC1 > ASIC3 [10].

Analytical, diagnostic and therapeutic context of Accn3

• By RT-PCR, one clone similar to the mouse Asic3 cDNA (proton-gated channel) was found mainly in the retina and cochlea, but its human ortholog was widely expressed [11].

References