Rich M M, Kraner S D, Barchi R L
Department of Neurology, Emory University School of Medicine, WMB Suite 6000, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Neurobiol Dis. 1999 Dec;6(6):515-22. doi: 10.1006/nbdi.1999.0257.
In rats treated with high-dose corticosteroids, skeletal muscle that is denervated in vivo (steroid-denervated) develops electrical inexcitability similar to that seen in patients with acute quadriplegic myopathy. To determine whether changes in muscle gene transcription might underlie inexcitability of steroid-denervated muscle we performed RNase protection assays to quantitate adult (SkM1) and embryonic (SkM2) sodium channel isoforms and chloride channel (CLC-1) mRNA levels in control, denervated, steroid-innervated, and steroid-denervated skeletal muscle. While SkM1 mRNA levels were relatively unaffected by denervation or steroid treatment, SkM2 mRNA levels were increased by both. These effects were synergistic and high levels of SkM2 mRNA were expressed in denervated muscle exposed to corticosteroids. Skeletal muscle CLC-1 mRNA levels were decreased by denervation. To better understand the marked upregulation of SkM2 in steroid-denervated muscle we examined changes in myogenin and glucocorticoid receptor mRNA levels. However, changes in these mRNA levels cannot account for the upregulation of SkM2 in steroid-denervated muscle.
在接受高剂量皮质类固醇治疗的大鼠中，体内失神经支配的骨骼肌（类固醇失神经支配）会出现电兴奋性丧失，类似于急性四肢瘫性肌病患者的情况。为了确定肌肉基因转录的变化是否可能是类固醇失神经支配肌肉兴奋性丧失的基础，我们进行了核糖核酸酶保护试验，以定量对照、失神经支配、类固醇神经支配和类固醇失神经支配骨骼肌中成人（SkM1）和胚胎（SkM2）钠通道亚型以及氯通道（CLC-1）的mRNA水平。虽然SkM1 mRNA水平相对不受失神经支配或类固醇治疗的影响，但SkM2 mRNA水平在两者作用下均升高。这些效应是协同的，并且在暴露于皮质类固醇的失神经支配肌肉中表达了高水平的SkM2 mRNA。失神经支配会降低骨骼肌CLC-1 mRNA水平。为了更好地理解类固醇失神经支配肌肉中SkM2的显著上调，我们检查了生肌调节因子和糖皮质激素受体mRNA水平的变化。然而，这些mRNA水平的变化并不能解释类固醇失神经支配肌肉中SkM2的上调。
