Altered gene expression in steroid-treated denervated muscle

Area of Science:

• Neuroscience
• Molecular Biology
• Physiology

Background:

• Corticosteroids and denervation can cause skeletal muscle electrical inexcitability.
• This condition resembles acute quadriplegic myopathy in humans.

Purpose of the Study:

• To investigate if altered gene transcription underlies the electrical inexcitability in steroid-denervated skeletal muscle.
• To quantify mRNA levels of specific sodium and chloride channel isoforms.

Main Methods:

• RNase protection assays were used to measure mRNA levels.
• Skeletal muscle from control, denervated, steroid-innervated, and steroid-denervated rats were analyzed.
• Levels of adult (SkM1) and embryonic (SkM2) sodium channel isoforms and chloride channel 1 (CLC-1) mRNA were quantified.

Main Results:

• Adult sodium channel (SkM1) mRNA levels were largely unaffected by denervation or steroid treatment.
• Embryonic sodium channel (SkM2) mRNA levels increased with both denervation and corticosteroid treatment.
• A synergistic increase in SkM2 mRNA was observed in steroid-denervated muscle.
• Chloride channel 1 (CLC-1) mRNA levels decreased following denervation.
• Changes in myogenin and glucocorticoid receptor mRNA did not explain SkM2 upregulation.

Conclusions:

• The study identifies a significant upregulation of the embryonic sodium channel isoform (SkM2) in steroid-denervated skeletal muscle.
• This upregulation of SkM2 mRNA is a key molecular event potentially contributing to the observed electrical inexcitability.
• Further research is needed to fully elucidate the mechanisms behind SkM2 upregulation in this model.