Sarcalumenin plays a critical role in age‐dependent reduction in cardiac function and SERCA2a activity

Abstract

Sarcalumenin (SAR), a Ca2+‐binding protein located in the longitudinal sarcoplasmic reticulum (SR), interacts with cardiac SR Ca2+‐ATPase(SERCA2a) to modulate its activity and expression. We have demonstrated that SAR deficiency resulted in mild cardiac dysfunction in young mice (JBC 2005). Since it is well known that SERCA2a activity is decreased with aging, we examined the effects of aging on cardiac function in SAR knockout mice (SAR‐KO). Cardiac function assessed by in vivo hemodynamic study and the expression levels of SERCA2a protein were progressively decreased in senescent SARKO (n=13) when compared with senescent wild‐type (WT) (n=12) or young SARKO (4month old, n=12). LV dp/dtmax (mmHg/s) was 3897 ± 134, 7091 ± 657, and 6836 ± 298 in senescent SARKO, senescent WT, and young SARKO, respectively. The expression levels of SERCA2a protein (% of young WT) were 28 ± 8, 84 ± 17, and 44 ± 17 in senescent SARKO, senescent WT, and young SARKO, respectively. Interestingly, downregulation of SAR preceded downregulation of SERCA in aging cardiac muscles of wild‐type mice. These findings indicated that SAR plays a critical role in age‐dependent reduction in cardiac function and SR Ca2+ reuptake.