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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 IC(50) 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.

Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode' s solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 micromol L(- 1)), but remained no change in the presence of Str (1 and 100 nmol L(-1)). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol L(-1)) , but had no obvious effects on the action of Str (10 micromol L(-1)). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 micromol L(-1)) or the removal of Ca2+ from Tyrode's solution. In Na+, K+ -free Tyrode' s solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 micromol L(-1)) was attenuated, while remained no change to Str (1 and 100 nmol L(-1)). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+ -free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+ -ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.