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.