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The mERG1a channel modulates skeletal muscle MuRF1, but not MAFbx, expression


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Introduction: We investigated the mechanism by which the MERG1a K+ channel increases ubiquitin proteasome proteolysis (UPP). Methods: Hindlimb suspension and electro-transfer of Merg1a cDNA into mouse gastrocnemius muscles induced atrophy. Results: Atrophic gastrocnemius muscles of hindlimb-suspended mice express Merg1a, Murf1, and Mafbx genes. Electrotransfer of Merg1a significantly decreases muscle fiber size (12.6%) and increases UPP E3 ligase Murf1 mRNA (2.1-fold) and protein (23.7%), but does not affect Mafbx E3 ligase expression. Neither Merg1a-induced decreased fiber size nor Merg1a-induced increased Murf1 expression is curtailed significantly by coexpression of inactive HR-Foxo3a, a gene encoding a transcription factor known to induce Mafbx expression. Conclusions: The MERG1a K+ channel significantly increases expression of Murf1, but not Mafbx. We explored this expression pattern by expressing inactive Foxo3a and showing that it is not involved in MERG1a-mediated expression of Murf1. These findings suggest that MERG1a may not modulate Murf1 expression through the AKT/FOXO pathway. Muscle Nerve 49:378–388, 2014