Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations.

Abstract

The purpose of this study was to determine the effect of amiodarone (Ami) on hERG-T618I currents in HEK293 cells. A transient transfection method was used to transfer hERG-T618I and hERG wild-type (WT) channel plasmids into HEK293 cells. An extracellular local perfusion method was used for administration. Currents were recorded using the whole-cell patch clamp technique. Ami (10 μM) had a greater retarding effect on the hERG-T618I channel than WT (P < 0.05). The half-inhibitory concentration for the mutant was approximately 1.82 times that of WT (P < 0.05). The WT current inhibition fraction against Ami was significantly greater than T618I in the same cell (P < 0.05). The STEP current of the mutant channel was larger than the WT channel, but the characteristic of inward rectification did not appear. Ami reduced the STEP current of the mutant channel, and the steady-state activation curve indicated that channel activation decreased (P > 0.05). Ami restored partial inactivation of the mutant channel. Ami effectively reduced the current in the phase 2 plateau (P < 0.05), but the phase 3 current did not exhibit the characteristics of a WT current. Ami inhibited hERG-T618I currents on HEK293 cells, but the effect was weaker than WT.