Mutations in the potassium channel encoded by the human ether-a-go-go-related gene (hERG) have been linked to inherited long QT syndrome (LQTS), a cardiac disease associated with an increased susceptibility to life-threatening ventricular arrhythmias and sudden death. Among these mutations, LQT2 mutation caused in cyclic nucleotide binding domain (CNBD) of hERG produce loss of function phenotypes and reduce IKr currents by defective protein trafficking. Here we tested whether trafficking defective mutants showing current have a difference in current inhibition by drugs (E4031, sparfloxacin). Methods: Ionic currents for F805C trafficking mutant were recorded in whole-cell patch-clamp technique. Results: One of trafficking defective mutants, hERG F805C trafficking mutants showed the current inhibition similar to WT at the high dose of E4031 and sparfloxacin. But, F805C hERG channel for E4031 and sparfloxacin appeared to have a resistance in current inhibition at the low dose of less than IC50 level. Conclusions: The present results suggest that the current of hERG trafficking mutants may have a different drug effect through conformational change of hERG structure or unknown protein trafficking mechanism.