Whitehead Nicholas P, Streamer Margaret, Lusambili Lynn I, Sachs Frederick, Allen David G
School of Medical Sciences and Institute for Biomedical Research, University of Sydney F13, Sydney, NSW, Australia.
Neuromuscul Disord. 2006 Dec;16(12):845-54. doi: 10.1016/j.nmd.2006.07.024. Epub 2006 Sep 26.
It is well-known that muscles from mdx mice are more susceptible to membrane damage from eccentric contractions than wild-type muscles. The present study tested the hypothesis that the stretch-induced membrane permeability in dystrophic muscle is due to Ca(2+) entry through stretch-activated channels (SACs) and the subsequent activation of Ca(2+) -dependent degradative pathways. Eccentric contractions were carried out on muscles from mdx and wild-type mice, both on isolated muscles and on intact mice subjected to downhill running on a treadmill. In isolated muscles the SAC blockers, streptomycin and GsMTx4, improved force and significantly reduced the uptake of procion orange dye into fibres from mdx muscles, which increased progressively over 60 min after the eccentric contractions. In experiments on intact mdx mice, streptomycin also partially prevented the reduced force and the increased membrane permeability (Evans Blue Dye uptake). The results suggest that Ca(2+) entry through SACs activates Ca(2+) -dependent pathways, which are the main cause of the increased membrane permeability in mdx muscle.
众所周知，与野生型肌肉相比，mdx小鼠的肌肉在离心收缩时更容易受到膜损伤。本研究检验了以下假设：营养不良肌肉中拉伸诱导的膜通透性是由于Ca(2+)通过拉伸激活通道（SACs）进入以及随后Ca(2+)依赖性降解途径的激活。对mdx和野生型小鼠的肌肉进行离心收缩实验，包括分离的肌肉以及在跑步机上进行下坡跑的完整小鼠。在分离的肌肉中，SAC阻滞剂链霉素和GsMTx4改善了肌力，并显著减少了mdx肌肉纤维中活性艳橙染料的摄取，这种摄取在离心收缩后60分钟内逐渐增加。在完整mdx小鼠的实验中，链霉素也部分预防了肌力下降和膜通透性增加（伊文思蓝染料摄取）。结果表明，Ca(2+)通过SACs进入激活了Ca(2+)依赖性途径，这是mdx肌肉膜通透性增加的主要原因。
