The modulation of sino-atrial node (SAN) automaticity is an essential mechanism of heart rate generation that is still not completely understood. Recent studies highlighted the importance of protein serotonylation by intracellular 5-HT during varies physiological actions. Nevertheless, the functional role of protein serotonylation in controlling SAN automaticity is largely unexplored. In this study, we screened. the cardiomyocytes proteins and found that sarco(endo)plasmic reticulum Ca ATPase type 2a (SERCA2a) can be serotonylated. Simulation studies using mathematical SAN cell model showed that variation of Ca2+ affinity of SERCA2a pump cause either tachycardia or bradycardia. (C) 2016 Elsevier Inc. All rights reserved.