I(to) reduction in HF ventricular myocytes is a commonly observed, while CaMKII activity is increased. We already reported that Kv4.3 overexpression significantly inhibits CaMKII activation in ventricular myocytes. Therefore, we suggested a role of Kv4.3 as a negative regulator for CaMKII activation. The aim of the present study was to investigate the effects of Kv4.3 on neonatal rat cardiomyocyte hypertrophy induced by norepinephrine (NE). Cardiomyocytes were infected with either Ad/GFP or Ad/Kv4.3 for 24 hrs, and then NE was added for 48h. Treatment of 20 M NE in Ad/GFP infected neonatal ventricular rat myocytes(NVRMs) induced increases in cell size, protein/DNA ratio, and atrial natriuretic factor expression, as wall as CaMKII activation. Moverover, a significant reduction of Kv4.3 expression was observed. Compared with Ad/GFP, the Ad/Kv4.3 overexpresison reversed NE-induced hypertrophy in NVRMs. This effect was accompanied by decrease in CaMKII activity. These results suggest that Kv4.3 might be act as suppressor of hypertrophic development in response to NE, possibly by inhibition of CaMKII activation.