Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Surg Res. 2019 Nov;243:130-142. doi: 10.1016/j.jss.2019.04.056. Epub 2019 Jun 4.
We previously demonstrated differential expression of nicotinic acetylcholine receptors (nAChRs) in the facial nerve-innervated orbicularis oris and somatic nerve-innervated gastrocnemius, which contribute to different sensitivities to muscle relaxants. Furthermore, the orbicularis oris exhibits less sensitivity to muscle relaxants after facial nerve injury, which is also related to upregulation of nAChRs. Here, we explored the regulatory mechanism for the different expression patterns. Because the agrin/Lrp4/MuSK/rapsyn and neuregulin1/ErbB signaling pathways are indispensable for maintaining the expression of nAChRs, we examined the activity of these two signaling pathways in gastrocnemius and orbicularis oris innervated by normal or injured facial nerves.
A quantitative analysis of these two signaling pathways was realized by immunofluorescence, and immunoprecipitation was applied to detect the level of phosphorylated MuSK in the gastrocnemius and orbicularis oris innervated by normal or injured facial nerves in adult rats.
ErbB and the phosphorylated MuSK were expressed more in orbicularis oris than in gastrocnemius (P < 0.05). No significant difference was found in the expression of agrin/Lrp4/MuSK/rapsyn. After facial nerve injury, the level of agrin and the percentage of phosphorylated MuSK decreased significantly, although the expression levels of MuSK, rapsyn, and neuregulin1/ErbB were highly upregulated.
Differential expression of the neuregulin1/ErbB signaling pathway may account for the different expression patterns of nAChRs at the neuromuscular junctions of the orbicularis oris and gastrocnemius. Overexpression of MuSK and rapsyn may contribute to upregulation of nAChRs after facial nerve injury.
我们之前的研究表明，面神经支配的口轮匝肌和躯体神经支配的腓肠肌中烟碱型乙酰胆碱受体（nAChRs）的表达存在差异，这导致它们对肌肉松弛剂的敏感性不同。此外，面神经损伤后面轮匝肌对肌肉松弛剂的敏感性降低，这也与 nAChRs 的上调有关。在这里，我们探讨了不同表达模式的调节机制。因为聚集蛋白/Lrp4/MuSK/rapsyn 和神经调节蛋白 1/ErbB 信号通路对于维持 nAChRs 的表达是必不可少的，所以我们检查了这些两条信号通路在正常或损伤面神经支配的腓肠肌和口轮匝肌中的活性。
通过免疫荧光定量分析了这两条信号通路，并应用免疫沉淀检测了正常或损伤面神经支配的成年大鼠腓肠肌和口轮匝肌中磷酸化 MuSK 的水平。
ErbB 和磷酸化 MuSK 在口轮匝肌中的表达高于腓肠肌（P<0.05）。聚集蛋白/Lrp4/MuSK/rapsyn 的表达没有明显差异。面神经损伤后，聚集蛋白的水平和磷酸化 MuSK 的百分比显著降低，尽管 MuSK、rapsyn 和神经调节蛋白 1/ErbB 的表达水平高度上调。
神经调节蛋白 1/ErbB 信号通路的差异表达可能是口轮匝肌和腓肠肌神经肌肉接头 nAChRs 表达模式不同的原因。MuSK 和 rapsyn 的过度表达可能有助于面神经损伤后 nAChRs 的上调。
