Department of Biomedical Sciences and Interdepartmental Research Center of Myology (cirMYO), University of Padova, Padova, Italy.
Department of Life Sciences, University of Trieste, Trieste, Italy.
J Gen Physiol. 2022 Nov 7;154(11). doi: 10.1085/jgp.202213128. Epub 2022 Sep 23.
Inositol 1,4,5-trisphosphate receptors (IP3Rs) are enriched at postsynaptic membrane compartments of the neuromuscular junction (NMJ), surrounding the subsynaptic nuclei and close to nicotinic acetylcholine receptors (nAChRs) of the motor endplate. At the endplate level, it has been proposed that nerve-dependent electrical activity might trigger IP3-associated, local Ca2+ signals not only involved in excitation-transcription (ET) coupling but also crucial to the development and stabilization of the NMJ itself. The present study was undertaken to examine whether denervation affects the subsynaptic IP3R distribution in skeletal muscles and which are the underlying mechanisms. Fluorescence microscopy, carried out on in vivo denervated muscles (following sciatectomy) and in vitro denervated skeletal muscle fibers from flexor digitorum brevis (FDB), indicates that denervation causes a reduction in the subsynaptic IP3R1-stained region, and such a decrease appears to be determined by the lack of muscle electrical activity, as judged by partial reversal upon field electrical stimulation of in vitro denervated skeletal muscle fibers.
三磷酸肌醇受体(IP3Rs)在神经肌肉接头(NMJ)的突触后膜区富集,围绕着突触核,并靠近运动终板的烟碱型乙酰胆碱受体(nAChRs)。在终板水平,有人提出神经依赖性电活动可能引发与 IP3 相关的局部 Ca2+信号,这些信号不仅参与兴奋转录(ET)偶联,而且对 NMJ 的自身发育和稳定也至关重要。本研究旨在探讨去神经支配是否会影响骨骼肌中的突触下 IP3R 分布,以及其潜在的机制。在体内去神经支配的肌肉(坐骨神经切断术后)和体外去神经支配的屈趾短肌(FDB)骨骼肌纤维上进行荧光显微镜检查,表明去神经支配导致突触下 IP3R1 染色区域减少,这种减少似乎是由肌肉电活动缺失引起的,因为体外去神经支配的骨骼肌纤维经场电刺激后部分逆转。