Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors
Shing-Hong Lin, Yuan-Ren Cheng, Robert W. Banks, Ming-Yuan Min, Guy S. Bewick
Nature Communications. 2016 May 10;7:11460
Speaker: Shi-Hong Ching (經士弘)
Commentator: Dr. Yang-Kao Wang (王仰高)
Date: 2017/04/21 4:00-4:50
Acid-sensing ion channel 3 (ASIC3) is one of the subunit for acid-sensing ion channel (ASIC), which involved in acid nociception. ASIC3 is mammalian homologue for epithelial sodium channel (ENaC), which has been demonstrated as essential mechanotransducers in C elegans and Drosophila1, suggesting ASIC3 has possible role in neurosensory mechanotransduction. Previous studies on ASIC3 mechanotransduction property have been disputed, owning to ASIC3’s heterogeneous expression in the dorsal root ganglion (DRG) neurons. In order to elucidate the role of ASIC3-containing channels in mechanotransduction, Asic3-knockout/eGFPf-knockin mice were used to characterize the heterogeneous expression of ASIC3 in the DRG. ASIC3 was found expressed majorly in parvalbumin (Pv+) expressing in DRG neurons and axons innervating muscle spindles, which are mechanoreceptors Specialized for Proprioception (proprioceptors). Floxed allele of Asic3 (Asic3f/f) were used to conditionally knockout ASIC3 expression in Pv+ DRG neurons, in order to probe the role of ASIC3 plays in mechanotransduction in these neurons. Neuronal response to localized elastic matrix movements, and muscle spindle electrophysiology response to muscle stretch were tested. Asic3 conditional knockout impaired mechanotransduction capability in Pv+ DRG neurons induced by substrate deformation-induced neurite stretching, which is required to transduce mechanical stimuli in proprioceptors. Asic3 conditional knockout also disrupted muscle spindle afferent sensitivity to dynamic stimuli. In behavioural tasks, when compared to wild type mice, conditional knockout mice showed increased foot faults during grid test, increased foot faults and longer time to complete in the narrowest balance beam walking tasks. In conclusion, ASIC3 plays an important role to dynamic mechanosensitivity in proprioceptors.