Mergla K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway

摘要: Skeletal muscle atrophy results from an imbalance in protein degradation and protein synthesis and occurs in response to injury, various disease states, disuse, and normal aging. Current treatments for this debilitating condition are inadequate. More information about mechanisms involved in the onset and progression of muscle atrophy is necessary for development of more effective therapies. Here we show that expression of the mouse ether‐a‐go‐go related gene (Mergla) K+ channel is up‐regulated in skeletal muscle of mice experiencing atrophy as a result of both malignant tumor expression and disuse. Further, ec‐topic expression of Mergla in vivo induces atrophy in healthy wt‐bearing mice, while expression of a dysfunctional Mergla mutant suppresses atrophy in hindlimb‐suspended mice. Treatment of hindlimb‐suspended mice with astemizole, a known Mergla channel blocker, inhibits atrophy in these …