The ERG1 Potassium Channel is Abundant in Cachectic Human Skeletal Muscle

Abstract

IntroductionA heteromultimer of the ERG1a/1b potassium channel is known to contribute to repolarization of the cardiac action potential. A homomultimer of the ERG1a subunit has been detected in the atrophying skeletal muscle of mice experiencing muscle disuse and cancer cachexia and has been shown to contribute to muscle atrophy by enhancing ubiquitin proteolysis; however, to our knowledge, ERG1 has not been reported in human skeletal muscle.Methods and ResultsHere, using immunohistochemistry we detect ERG1 immunofluorescence at low levels in Rectus abdominis muscle of young adult humans and show that it trends toward greater levels (10.6%) in the same muscle of healthy aged adults. Further, we detect ERG1 immunofluorescence at a statistically greater level (53.6%; p<0.05) in the Rectus abdominis muscle of older people having cancer cachexia than in age‐matched adults. Additionally, we observe ERG1 immunofluorescence in skeletal muscle sarcolemma and detect that its fluorescent pattern is consistent with I‐band localization.DiscussionThe data suggest that ERG1 may be related to muscle loss in humans and may be located in t‐tubules where it could influence calcium handling.Support or Funding InformationThis work was supported in part by Southern Illinois University School of Medicine (Research Seed Grant to ALP). The work was also supported in part by the Italian Society for Cancer Research (AIRC grant number 17388 to M Sandri) and by Austrian national co‐financing of the Austrian Federal Ministry of Science and Research; Ludwig Boltzmann Society (Vienna, Austria) to H Kern. PK would like to acknowledge National Science Foundation (CHE 0748676), NIH (GM 106364) for partial financial support of this research. The authors wish to thank Dr. Don Caspary who graciously provided FBN rat muscles. Human Pectoralis minor muscle samples were provided by the SIU School of Medicine Tissue Bank, a Simmons Cancer Institute funded program. Other investigators may have received samples from these same tissue specimens. UC thanks the IRCCS Fondazione Ospedale San Camillo, Venezia, Italy and the A&C M‐C Foundation for Translational Research for scientific support.