The human ether-à-go-go-related gene (HERG) encodes the pore-forming subunit of 
the rapidly activating delayed rectifier potassium channel in the heart. We 
previously showed that HERG channel protein is modified by N-linked 
glycosylation. HERG protein sequence contains two extracellular consensus sites 
for N-linked glycosylation (N598, N629). In this study, we used the approaches 
of site-directed mutagenesis and biochemical modification to inhibit N-linked 
glycosylation and studied the role of glycosylation in the cell surface 
expression and turnover of HERG channels. Our results show that N598 is the only 
site for N-linked glycosylation and that glycosylation is not required for the 
cell surface expression of functional HERG channels. In contrast, N629 is not 
used for glycosylation, but mutation of this site (N629Q) causes a protein 
trafficking defect, which results in its intracellular retention. Pulse-chase 
experiments show that the turnover rate of nonglycosylated HERG channel is 
faster than that of the glycosylated form, suggesting that N-linked 
glycosylation plays an important role in HERG channel stability.