title: 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.
authors.affiliation: Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, 07103, USA.
authors.forename: Lai-Hua
authors.initials: LH
authors.lastname: Xie
authors.forename: Mayilvahanan
authors.initials: M
authors.lastname: Shanmugam
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Park
authors.forename: Zhenghang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Hairuo
authors.initials: H
authors.lastname: Wen
authors.forename: Bin
authors.initials: B
authors.lastname: Tian
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: Gopal J
authors.initials: GJ
authors.lastname: Babu
mesh_terms: D000200:Action Potentials; D000375:Aging / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016275:Atrial Function; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D005838:Genotype; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D010641:Phenotype; D011510:Proteolipids / Q000172:deficiency* / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013997:Time Factors
chemical_list: D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D011510:Proteolipids; C077258:sarcolipin; D003094:Collagen; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases