Decreased sarcolipin protein expression and enhanced sarco(endo)plasmic reticulum Ca 2+ uptake in human atrial fibrillation

Abstract

Sarcolipin (SLN), a key regulator of cardiac sarco(endo)plasmic reticulum (SR) Ca 2+ ATPase, is predominantly expressed in atria and mediates β-adrenergic responses. Studies have shown that SLN mRNA expression is decreased in human chronic atrial fibrillation (AF) and in aortic banded mouse atria; however, SLN protein expression in human atrial pathology and its role in atrial SR Ca 2+ uptake are not yet elucidated. In the present study, we determined the expression of major SR Ca 2+ handling proteins in atria of human AF patients and in human and in a mouse model of heart failure (HF). We found that the expression of SR Ca 2+ uptake and Ca 2+ release channel proteins are significantly decreased in atria but not in the ventricles of pressure-overload induced HF in mice. In human AF and HF, the expression of SLN protein was significantly decreased; whereas the expressions of other major SR Ca 2+ handling proteins were not altered. Further, we found that the SR Ca 2+ uptake was significantly increased in human AF. The selective downregulation of SLN and enhanced SR Ca 2+ uptake in human AF suggest that SLN downregulation could play an important role in abnormal intracellular Ca 2+ cycling in atrial pathology.