Ether-a-go-go related gene-1a potassium channel abundance varies within specific skeletal muscle fiber type

  • Luke B. Anderson Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, United States.
  • Chase D. Latour Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States.
  • Omar Khader Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, United States.
  • Bryce H. Massey Brown University, Providence, RI, United States.
  • Brittan Cobb Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, United States.
  • Amber L. Pond | apond@siumed.edu Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, United States.

Abstract

The ERG1A K+ channel, which is partially responsible for repolarization of the cardiac action potential, has also been reported in skeletal muscle where it modulates ubiquitin proteolysis. Because ERG1A protein appears variably expressed in muscles composed of mixed fiber types, we hypothesized that its abundance in skeletal muscle might differ with fiber type. Indeed, skeletal muscle fibers vary in speed of contraction (fast or slow), which is mainly determined by myosin heavy chain (MyHC) isoform content, but a sarcolemmal K+ channel might also modulate contraction speed. To test our hypothesis, we cryo-sectioned Soleus (SOL), Extensor Digitorum Longus (EDL), and Gastrocnemius muscles from five rats. These muscles were chosen because the SOL and EDL contain an abundance of slow- and fast-twitch fibers, respectively, while the Gastrocnemius has a more heterogeneous composition. The muscle sections were co-immunostained for the ERG1A protein and either the fast- or slow-twitch MyHC to identify fiber type. ERG1A fluorescence was then measured in the sarcolemma of each fiber type and compared. The data reveal that the ERG1A protein is more abundant in the fibers of the SOL than in the EDL muscles, suggesting ERG1A may be more abundant in the slow than the fast fibers, and this was confirmed with immunoblot. However, because of the homogeneity of fiber type within these muscles, it was not possible to get enough data from both fiber types within a single muscle to compare ERG1A composition within fiber type. However, immunohistochemistry of sections from the fiber type heterogeneous Gastrocnemius muscle reveals that slow fibers had, on average, a 17.2% greater ERG1A fluorescence intensity than fast fibers (p<0.03). Further, immunoblot reveals that ERG1A protein is 41.6% more abundant (p=0.051) in old than in young rat Gastrocnemius muscle. We postulate that this membrane bound voltage-gated channel may affect membrane characteristics, the duration of the action potential generated, and/or the speed of contraction. Indeed, ERG1A protein is more abundant in aged and atrophic skeletal muscle, both of which exhibit slower rates of contraction.

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Published
2019-09-12
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Original Articles
Supporting Agencies
SIU REACH Award (to LBA) from the Southern Illinois University (SIU) Office of the Vice Chancellor for Research, SIU School of Medicine Seed Grant to Amber L. Pond
Keywords:
Ether-a-go-go related gene, skeletal muscle, atrophy, muscle fiber type
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How to Cite
Anderson, L., Latour, C., Khader, O., Massey, B., Cobb, B., & Pond, A. (2019). Ether-a-go-go related gene-1a potassium channel abundance varies within specific skeletal muscle fiber type. European Journal of Translational Myology, 29(3). https://doi.org/10.4081/ejtm.2019.8402