Department of Life Science, National Taiwan University, Taipei 10090, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Int J Mol Sci. 2023 Aug 14;24(16):12783. doi: 10.3390/ijms241612783.
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 () were indentation depth-dependent and significantly inhibited by mild acidification (pH 7.2~6.8). The acid-inhibiting effect occurred in neurons with an sensitive to APETx2 (an ASIC3-selective antagonist) inhibition, but not in those with an resistant to APETx2. Detailed subgroup analyses revealed 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 () 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 and among Pv+ proprioceptors. In conclusion, our findings highlight the importance of ASIC3-containing ion channels in the physiological response of proprioceptors to acidic environments.
本体感受器是一种低阈值机械感受器，参与感知身体姿势和应变承载。然而，本体感受器对疲劳和肌肉酸中毒相关干扰的生理反应仍不清楚。在这里，我们采用全细胞膜片钳记录技术，研究了轻度酸中毒对小鼠背根神经节（DRG）本体感受神经元机械敏感性的影响。我们在层粘连蛋白包被的弹性基质上培养带有神经突的钙调蛋白阳性（Pv+）DRG 神经元，并通过基质变形驱动神经突拉伸（SDNS）来检测机械激活电流。SDNS 诱导的内向电流（）与压痕深度有关，并且被轻度酸化（pH 7.2~6.8）显著抑制。这种酸化抑制作用发生在对 APETx2（ASIC3 选择性拮抗剂）抑制敏感的神经元中，但不在对 APETx2 有抗性的神经元中。详细的亚组分析显示，有 敏感的神经元（59%（25/42））表达，其中 90%的神经元对 APETx2 抑制敏感。相比之下，pH 6.8 诱导的电流（）在 90%（42/42）的 Pv+DRG 神经元中表达，其中 59%（21/32）的神经元对 APETx2 抑制敏感。总之，ASIC3 包含的通道高度异质，并且在 Pv+本体感受器的和之间有不同的贡献。综上所述，我们的研究结果强调了 ASIC3 包含的离子通道在本体感受器对酸性环境的生理反应中的重要性。
