We investigated the effects of AT1 receptor stimulation by angiotensin II (Ang 
II) on human ether-a-go-go-related gene (hERG) potassium channel protein in a 
heterogeneous expression system with the human embryonic kidney (HEK) 293 cells 
which stably expressed hERG channel protein and were transiently transfected 
with the human AT1 receptors (HEK293/hERG). Western-blot analysis showed that 
Ang II significantly decreased the expression of mature hERG channel protein 
(155-kDa band) in a time- and dose-dependent manner without affecting the level 
of immature hERG channel protein (135-kDa band). The relative intensity of 
155-kDa band was 64.7±6.8% of control (P<0.01) after treatment of Ang II at 
100nM for 24h. To investigate the effect of Ang II on the degradation of mature 
hERG channel protein, we blocked forward trafficking from ER to Golgi with a 
Golgi transit inhibitor brefeldin A (10μM). Ang II significantly enhanced the 
time-dependent reduction of mature hERG channel protein. In addition, the 
proteasomal inhibitor lactacystin (5μM) inhibited Ang II-mediated the reduction 
of mature hERG channel protein, but the lysosomal inhibitor bafilomycin A1 (1μM) 
had no effect on the protein. The protein kinase C (PKC) inhibitor 
bisindolylmaleimide 1 (1μM) antagonized the reduction of mature hERG channel 
protein induced by Ang II. The results indicate that sustained stimulation of 
AT1 receptors by Ang II reduces the mature hERG channel protein via accelerating 
channel proteasomal degradation involving the PKC pathway.