α-mannosidase I-dependent N-linked glycosylation affects hERG channel functional availability during reactivation.

Asparagine-linked (N-linked) glycosylation has emerged as an essential post-translational modification to control the number of channels embedded in the plasma membrane as well as to regulate their functional gating properties. The aim of this study was to evaluate the exact role of α-mannosidase I-dependent N-linked glycosylation process in Golgi apparatus on the human rapidly activating delayed rectifier potassium channel, hERG channel. In the heterologous expression system in HEK293 cells, kifunensine, a selective inhibitor of class I α-mannosidase, does not significantly reduce hERG channel current (IhERG) when applied for 48 h. However, kifunensine selectively reduced the reactivation current of the hERG channel, while activation, inactivation and deactivation kinetics were not detectably affected by kifunensine. Our results suggest that α-mannosidase I-dependent N-linked glycosylation in the Golgi apparatus plays a key role in regulating hERG functional availability during reactivation.