Calcium Signaling in Skeletal Muscle Atrophy: A Novel Role for the ERG1alpha K+ Channel
Abstract
The ERG1A potassium channel is up-regulated in atrophic skeletal muscle and increases proteolysis when it is ectopically expressed in muscle. We have shown that, when it is expressed in cultured C2C12 myotubes, ERG1A increases the basal intracellular calcium concentration; however, the mechanism by which this occurs and the consequences of this are not known. Thus, we proposed to investigate the mechanism by which ERG1A increases intracellular calcium and the downstream effect of this on calpain enzyme-mediated proteolysis. We have now completed all Major Tasks. Major Task 1. We have determined that the increase in intracellular calcium is not a consequence of ERG1A modulation of L-type calcium channel gene expression or protein abundance nor modulation of L-type calcium channel conductance; nor is it a result of modulation of store operated calcium entry (SOCE). However, our data shows that the source of the HERG-induced calcium increase is intracellular stores through modulation of both IP3 signaling and ryanodine receptor channel activity. Major Task 2. We have determined that ERG1A does increase calpain activity mainly as a result of the increased calcium concentration and also a decrease in calpastatin protein abundance. Major Task 3. We prepared samples for Next Generation Sequencing which was completed. We viewed this large set of data and denoted certain ERG1-modulated gene sets of interest which has included members of both the IP3 and RYR1 signaling cascades, the retinol pathway, and modulators of reactive oxygen species. We have confirmed modulation of genes encoding members of the RYR and retinol pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2022
- Accession Number
- AD1176298
Entities
People
- Amber L Pond
- Gregory H. Hockerman
Organizations
- Purdue University
- Southern Illinois University Carbondale