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The effects of rapid electrical stimulation (RES) of contraction on the gap junction remodeling are not well-understood. METHODS Neonatal rat ventricular myocytes cultured for 5 days were subjected to RES at 3.0 Hz for up to 120 min. RESULTS RES resulted in a significant upregulation of Cx43. Angiotensin II content was increased significantly by RES\u003e15 min. Phosphorylated forms of extracellular signal-regulated protein kinase (ERK), c-Jun NH_2-terminal kinases (JNK) and p38 mitogen-activated protein kinases (p38 MAPKs) were all increased dramatically by RES with peaks at 5\uff5e60 min. Propagation of excitation was visualized by extracellular potential mapping by using a multiple electrode array system. Conduction velocity was increased significantly by RES for 60 to 90 min. Treatment of myocytes with losartan prevented most of these effects of RES. RES-induced upregulation of Cx43 was also prevented by specific inhibitors for ERK and p38 MAPKs. 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