Abstract: We studied the effects of the lidocaine on the hERG K⁺ channels with a focus on the electrophysiology of the heart. The hERG current was recorded using the conventional whole-cell patch clamp technique and the channel protein expression level was measured with Western blot in HEK 293 cells stablely expressed hERG K⁺ channels. The langendorff perfusion system was used to record the ECG from isolated rabbit heart. Lidocaine inhibited hERG current in a concentration-dependent manner at 0.3-1 000 μmol·L^-1, the IC₅₀ value was 88.63±7.99 μmol·L^-1. The inhibitory action was enhanced by positive votalge without changing the votalge-dependent activation of the channel. However, lidocaine inhibited hERG current in a frequency-dependent manner. In addition, chronic incubation of lidocaine did not change the hERG K⁺ channel protein expression. ECG recordings in the isolated perfused rabbit heart demonstrated that lidocaine (> 100 μmol·L^-1) did not affected QTc interval, but decreased the heart rate and prolonged the PR interval and QRS duration. Our results demonstrate that lidocaine potentially inhibits the hERG K⁺ current at a high concentration, but does not prolonged the QTc of ECG.