Suppression of sodium channel function in differentiating C2 muscle cells stably overexpressing rat androgen
J S Tabb1, G R Fanger, E M Wilson
1Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755-3833.
Abstract:
Differentiation of skeletal muscle and the formation of the neuromuscular junction are regulated by steroid hormones. The effects of androgens on ion channel proteins central to neuromuscular signalling have been investigated in differentiating mouse muscle C2 cells and in C2 cells that stably overexpress the rat androgen receptor (AR) cDNA. Neither the expression nor function of ACh receptors was regulated by androgenic actions in these cells. However, voltage-dependent sodium (Na) current density was decreased by androgen treatment of C2 cells and was abolished, even in the absence of androgens, in C2 cells that overexpress the AR. The decrease in functional Na current was not accompanied by concomitant decreases in Na channel mRNA, suggesting that AR influence posttranscriptional processing of Na channels in differentiating C2 cells.
Insights
Androgens impact skeletal muscle by reducing sodium channel function, not affecting acetylcholine receptors. This suggests androgen receptors influence sodium channel processing after gene transcription.
Area of Science:
- Neuroscience
- Endocrinology
- Muscle Physiology
Background:
- Steroid hormones, particularly androgens, play a role in skeletal muscle differentiation and neuromuscular junction formation.
- Ion channel proteins are critical for neuromuscular signaling.
Purpose of the Study:
- To investigate the effects of androgens on ion channel proteins involved in neuromuscular signaling.
- To examine these effects in differentiating mouse muscle C2 cells and in cells overexpressing the androgen receptor (AR).
Main Methods:
- Utilized differentiating mouse muscle C2 cells.
- Employing C2 cells engineered to stably overexpress the rat androgen receptor (AR) cDNA.
- Assessed the expression and function of acetylcholine receptors and voltage-dependent sodium channels.
Main Results:
- Androgenic actions did not alter the expression or function of acetylcholine receptors.
- Voltage-dependent sodium (Na) current density was reduced by androgen treatment in C2 cells.
- Sodium current was abolished in AR-overexpressing cells, even without androgens.
- The reduction in Na current was not linked to decreased Na channel mRNA levels.
Conclusions:
- Androgen receptor (AR) signaling influences sodium channel function in differentiating skeletal muscle.
- AR appears to affect posttranscriptional processing of sodium channels, rather than transcription.
- These findings highlight a novel regulatory mechanism of neuromuscular signaling by androgens.
