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.