Unknown

Dataset Information

0

Ablation of sarcolipin results in atrial remodeling.


ABSTRACT: Sarcolipin (SLN) is a key regulator of sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase (SERCA), and its expression is altered in diseased atrial myocardium. To determine the precise role of SLN in atrial Ca(2+) homeostasis, we developed a SLN knockout (sln-/-) mouse model and demonstrated that ablation of SLN enhances atrial SERCA pump activity. The present study is designed to determine the long-term effects of enhanced SERCA activity on atrial remodeling in the sln-/- mice. Calcium transient measurements show an increase in atrial SR Ca(2+) load and twitch Ca(2+) transients. Patch-clamping experiments demonstrate activation of the forward mode of sodium/calcium exchanger, increased L-type Ca(2+) channel activity, and prolongation of action potential duration at 90% repolarization in the atrial myocytes of sln-/- mice. Spontaneous Ca(2+) waves, delayed afterdepolarization, and triggered activities are frequent in the atrial myocytes of sln-/- mice. Furthermore, loss of SLN in atria is associated with increased interstitial fibrosis and altered expression of genes encoding collagen and other extracellular matrix proteins. Our results also show that the sln-/- mice are susceptible to atrial arrhythmias upon aging. Together, these findings indicate that ablation of SLN results in increased SERCA activity and SR Ca(2+) load, which, in turn, could cause abnormal intracellular Ca(2+) handling and atrial remodeling.

SUBMITTER: Xie LH 

PROVIDER: S-EPMC3378074 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Ablation of sarcolipin results in atrial remodeling.

Xie Lai-Hua LH   Shanmugam Mayilvahanan M   Park Ji Yeon JY   Zhao Zhenghang Z   Wen Hairuo H   Tian Bin B   Periasamy Muthu M   Babu Gopal J GJ  

American journal of physiology. Cell physiology 20120411 12


Sarcolipin (SLN) is a key regulator of sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase (SERCA), and its expression is altered in diseased atrial myocardium. To determine the precise role of SLN in atrial Ca(2+) homeostasis, we developed a SLN knockout (sln-/-) mouse model and demonstrated that ablation of SLN enhances atrial SERCA pump activity. The present study is designed to determine the long-term effects of enhanced SERCA activity on atrial remodeling in the sln-/- mice. Calcium transient m  ...[more]

Similar Datasets

2010-11-01 | E-GEOD-23403 | biostudies-arrayexpress
2010-11-01 | GSE23403 | GEO
| S-EPMC2077025 | biostudies-literature
| S-EPMC3020129 | biostudies-literature
| S-EPMC4086672 | biostudies-literature
| S-EPMC8207433 | biostudies-literature
| S-EPMC4979747 | biostudies-literature
| S-EPMC11010019 | biostudies-literature
| S-EPMC5265852 | biostudies-literature
| S-EPMC8999753 | biostudies-literature