ERG1 encodes a K+ channel partially responsible for cardiac action potential repolarization in humans and mice. The Pond laboratory has shown that the ERG1 channel participates in the onset of skeletal muscle (skm) atrophy (muscle loss) by increasing ubiquitin proteasome proteolysis (UPP) activity and that ERG1 up-regulation induces expression of MuRF1, a UPP ligase. Here, we explore the mechanism. It is known that Murf1 expression is linked to activation of NF-kB transcription factor family members by upstream IKK-b activation. We hypothesized, therefore, that ERG1 expression may induce NF-kB activity. Thus, we ectopically co-expressed mouse ERG1 (MERG1) and an NF-kB activity luciferase reporter in left gastrocnemius muscles of mice while co-expressing the NF-kB reporter and a control empty plasmid in the right gastrocnemius muscles (n=40). We humanely killed 5 mice daily and harvested all gastrocnemius muscles everyday starting at Day 0 and continuing through Day 7. The data show that MERG1 expression decreases NF-kB activity in contrast to expectations. Specifically, the NF-kB activity decreased 40.6% after the first 24 hours and dropped by 65% on day 3 after which the activity began to increase, reaching levels not statistically different from Day 0 control levels by Days 6 and 7. This is surprising because NF-kB factors are known to induce expression of atrophy-related genes. We conclude that, because MERG1a expression causes a significant decrease in NF-kB transcription factor activity, the MERG1a K+ channel does not modulate expression of the MuRF1 E3 ligase through NF-kB transcription factors nor ultimately through the IKK-b/IkB-a/NF-kB pathway.