KOPS - The Institutional Repository of the University of Konstanz

Effect of Calstabin1 Depletion on Calcium Transients and Energy Utilization in Muscle Fibers and Treatment Opportunities with RyR1 Stabilizers

Effect of Calstabin1 Depletion on Calcium Transients and Energy Utilization in Muscle Fibers and Treatment Opportunities with RyR1 Stabilizers

Cite This

Files in this item

Checksum: MD5:0fd393bb5d08864bc1ea4738ee5fbea5

BRECKNER, Anke, Magdalena GANZ, David MARCELLIN, Jens RICHTER, Nicole GERWIN, Martin RAUSCH, 2013. Effect of Calstabin1 Depletion on Calcium Transients and Energy Utilization in Muscle Fibers and Treatment Opportunities with RyR1 Stabilizers. In: PLoS one. 8(11), e81277. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0081277

@article{Breckner2013-11-26Effec-42245, title={Effect of Calstabin1 Depletion on Calcium Transients and Energy Utilization in Muscle Fibers and Treatment Opportunities with RyR1 Stabilizers}, year={2013}, doi={10.1371/journal.pone.0081277}, number={11}, volume={8}, journal={PLoS one}, author={Breckner, Anke and Ganz, Magdalena and Marcellin, David and Richter, Jens and Gerwin, Nicole and Rausch, Martin}, note={Article Number: e81277} }

eng Effect of Calstabin1 Depletion on Calcium Transients and Energy Utilization in Muscle Fibers and Treatment Opportunities with RyR1 Stabilizers Ganz, Magdalena Richter, Jens Breckner, Anke Richter, Jens Ganz, Magdalena Gerwin, Nicole Rausch, Martin Rausch, Martin Depletion of calstabin1 (FKBP12) from the RyR1 channel and consequential calcium leakage from the sarcoplasmic reticulum (SR) is found in certain disease conditions such as dystrophy, aging or muscle overuse. Here, we first assessed the effect of calstabin1 depletion on resting Ca<sup>2+</sup> levels and transients. We found that depletion of calstabin1 with the calstabin1-dissociation compound FK506 increased the release of calcium from the SR by 14 % during tetanic stimulation (50 Hz, 300 ms) and delayed cytosolic calcium removal. However, we did not find a significant increase in resting cytosolic Ca<sup>2+</sup> levels. Therefore, we tested if increased SERCA activity could counterbalance calcium leakage. By measuring the energy utilization of muscle fibers with and without FK506 treatment, we observed that FK506-treatment increased oxygen consumption by 125% compared to baseline levels. Finally, we found that pretreatment of muscle fibers with the RyR1 stabilizer JTV-519 led to an almost complete normalization of calcium flux dynamics and energy utilization. We conclude that cytosolic calcium levels are mostly preserved in conditions with leaky RyR1 channels due to increased SERCA activity. Therefore, we suggest that RyR1 leakiness might lead to chronic metabolic stress, followed by cellular damage, and RyR1 stabilizers could potentially protect diseased muscle tissue. Gerwin, Nicole 2013-11-26 2018-05-03T11:27:48Z Attribution 3.0 Unported Breckner, Anke Marcellin, David Marcellin, David 2018-05-03T11:27:48Z

Downloads since May 3, 2018 (Information about access statistics)

Breckner_2-189och74002q66.pdf 212

This item appears in the following Collection(s)

Attribution 3.0 Unported Except where otherwise noted, this item's license is described as Attribution 3.0 Unported

Search KOPS


Browse

My Account