Probing the Effect of Acidosis on Tether-Mode Mechanotransduction of Proprioceptors.
Yuan-Ren ChengChih-Hung ChiCheng-Han LeeShing-Hong LinMing-Yuan MinChih-Cheng ChenPublished in: International journal of molecular sciences (2023)
Proprioceptors are low-threshold mechanoreceptors involved in perceiving body position and strain bearing. However, the physiological response of proprioceptors to fatigue- and muscle-acidosis-related disturbances remains unknown. Here, we employed whole-cell patch-clamp recordings to probe the effect of mild acidosis on the mechanosensitivity of the proprioceptive neurons of dorsal root ganglia (DRG) in mice. We cultured neurite-bearing parvalbumin-positive (Pv+) DRG neurons on a laminin-coated elastic substrate and examined mechanically activated currents induced through substrate deformation-driven neurite stretch (SDNS). The SDNS-induced inward currents ( I SDNS ) were indentation depth-dependent and significantly inhibited by mild acidification (pH 7.2~6.8). The acid-inhibiting effect occurred in neurons with an I SDNS sensitive to APETx2 (an ASIC3-selective antagonist) inhibition, but not in those with an I SNDS resistant to APETx2. Detailed subgroup analyses revealed I SDNS was expressed in 59% (25/42) of Parvalbumin-positive (Pv+) DRG neurons, 90% of which were inhibited by APETx2. In contrast, an acid (pH 6.8)-induced current ( I Acid ) was expressed in 76% (32/42) of Pv+ DRG neurons, 59% (21/32) of which were inhibited by APETx2. Together, ASIC3-containing channels are highly heterogenous and differentially contribute to the I SNDS and I Acid among Pv+ proprioceptors. In conclusion, our findings highlight the importance of ASIC3-containing ion channels in the physiological response of proprioceptors to acidic environments.
Keyphrases
- spinal cord
- high glucose
- diabetic rats
- drug induced
- single cell
- endothelial cells
- randomized controlled trial
- skeletal muscle
- type diabetes
- magnetic resonance
- magnetic resonance imaging
- signaling pathway
- stem cells
- oxidative stress
- bone marrow
- high resolution
- quantum dots
- optical coherence tomography
- physical activity
- depressive symptoms
- stress induced
- high fat diet induced
- single molecule
- wild type