Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a 
(SERCA2a) and is expressed abundantly in atria. In this study we investigated 
the physiological significance of sarcolipin in the heart by generating a mouse 
model deficient for sarcolipin. The sarcolipin-null mice do not show any 
developmental abnormalities or any cardiac pathology. The absence of sarcolipin 
does not modify the expression level of other Ca2+ handling proteins, in 
particular phospholamban, and its phosphorylation status. Calcium uptake studies 
revealed that, in the atria, ablation of sarcolipin resulted in an increase in 
the affinity of the SERCA pump for Ca2+ and the maximum velocity of Ca2+ uptake 
rates. An important finding is that ablation of sarcolipin resulted in an 
increase in atrial Ca2+ transient amplitudes, and this resulted in enhanced 
atrial contractility. Furthermore, atria from sarcolipin-null mice showed a 
blunted response to isoproterenol stimulation, implicating sarcolipin as a 
mediator of beta-adrenergic responses in atria. Our study documented that 
sarcolipin is a key regulator of SERCA2a in atria. Importantly, our data 
demonstrate the existence of distinct modulators for the SERCA pump in the atria 
and ventricles.