Disease relevance of Accn1

• Using the neuronal cell body as a model of the sensory terminal we investigated if ASIC2 or 3 contributed to mechanically activated currents in dorsal root ganglion (DRG) neurones [1].
• The presence of ASIC2 in SG neurons could provide sensors to directly convert local acidosis to excitatory responses, therefore offering a cellular mechanism linking hearing losses caused by many enigmatic causes (e.g., ischemia or inflammation of the inner ear) to excitotoxicity [2].
• ASIC2 null mice showed no significant hearing loss, indicating that the ASIC2 was not directly involved in the mechanotransduction of the mammalian cochlea [2].

High impact information on Accn1

• Here we show that disrupting the mouse BNC1 gene markedly reduces the sensitivity of a specific component of mechanosensation: low-threshold rapidly adapting mechanoreceptors [3].
• Consistent with this function, we found BNC1 in the lanceolate nerve endings that lie adjacent to and surround the hair follicle [3].
• Although BNC1 has been proposed to have a role in pH sensing, the acid-evoked current in cultured sensory neurons and the response of acid-stimulated nociceptors were normal in BNC1 null mice [3].
• To test the contribution of each subunit, we studied DRG from three strains of mice, each bearing a targeted disruption of BNC1, ASIC, or DRASIC [4].
• Members of the BNaC/ASIC family of ion channels have been implicated in mechanotransduction and nociception mediated by dorsal root ganglion (DRG) neurons [5].

Biological context of Accn1

• Here we have investigated whether the ASIC2 sodium channel, recently shown by us to be necessary for normal SAM sensitivity, might be regulated by BDNF and thus partially account for the down-regulation of SAM sensitivity seen in BDNF deficient mice [6].
• No differences in current amplitude or kinetics were found between ASIC2 and/or ASIC3 null mutants and controls [1].
• Inactivation of the ASIC2 gene in mice leads to an increase in the rod electroretinogram a- and b-waves and thus to an enhanced gain of visual transduction [7].

Anatomical context of Accn1

• Surprisingly, we did not detect mRNA for ASIC2 in mouse taste buds, although we readily observed its expression in rat taste buds [8].
• Together, these data suggest that ASIC2 contributes to suprathreshold functions of the cochlea [2].
• Acid-sensing ion channel 2 contributes a major component to acid-evoked excitatory responses in spiral ganglion neurons and plays a role in noise susceptibility of mice [2].

Other interactions of Accn1

• However, the specific contribution of ASIC1 and ASIC2 subunits to acid-evoked currents in hippocampal neurons remained uncertain [9].
• QPCR of whole thoracolumbar DRG revealed and abundance of ASIC2 > ASIC1 > ASIC3 [10].
• Acid-sensing ion channel 2 is important for retinal function and protects against light-induced retinal degeneration [7].

References