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Accession Number:

AD1151192

Title:

Calcium Signaling in Skeletal Muscle Atrophy: A Novel Role for the ERG1alpha K+ Channel

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Author Organization(s):

Report Date:

2021-07-01

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. We proposed to investigate the mechanism by which ERG1A increases intracellular calcium and the downstream effect of this on calpain enzyme-mediated proteolysis. To date, we have completed Major Task 2, determining that ERG1A does increase calpain activity mainly as a result of the increased calcium concentration and also a decrease in calpastatin protein abundance. We have completed approximately 95% of Major Task 1, determining that the increase in calcium is not a consequence of ERG1A modulation of L-type calcium channel gene expression or protein abundance or modulation of L-type calcium channel conductance or ryanodine receptor activity; but that the source of the calcium is intracellular stores through IP3 signaling and likely also by HERG-membrane modulation of T-type calcium channel activity. Finally, we have completed about 75% of Major Task 3, having prepped samples for Next Generation Sequencing which has been completed. We have viewed this large set of data and denoted certain ERG1-modulated gene sets which are of interest. We have identified some oligo sets for quantitative PCR and determined the efficiency of a few. We have noted that IGF1 expression is indeed down regulated by ERG1A.

Pages:

39

File Size:

2.58MB

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Distribution Statement:

Approved For Public Release

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