Abnormalities in intracellular Ca2+ handing are believed to contribute to arrhythmogenesis during atrial fibrillation (AF). Ca2+/calmodulin-dependent protein kinaseII delta (CaMKII delta) overexpression was detected in atrial myocytes from patients and animal models with persistent AF. In the present study, we found that rapid electrical field stimulation applied to primary atrial myocytes altered the CaMKII delta activity, not expression level, resulting in Ca2+ disorder. By lentivirus mediated delivery of CaMKII delta gene or siRNA into atrial myocytes, cells with different CaMKII delta expression were generated. Changes of CaMKII delta expression altered the sarcoplasmic reticulum (SR) Ca2+ release and L-type Ca2+ channels current (I-Ca) in both steady and electrical stimulating state. These results revealed the important role of CaMKII delta in Ca2+ disorder caused by electrical field stimulation. It also provided a potential method to improve Ca2+ disorder in AF by modulating CaMKII delta expression level. (C) 2011 Elsevier Inc. All rights reserved.