Aim: To examine the effects of ginseng saponins on the heterologously expressed human ether-a-go-go related gene (HERG) that encodes the rapid component of the delayed rectifier K + channel. Methods: A two-electrode voltage clamp technique was used. HERG currents were recorded in Xenopus oocytes injected with HERG cRNA. Results: Crude saponins of Korean red ginseng (GS) induced a minimal increase of the maximal HERG conductance without changes in the voltage-dependent HERG current activation and inactivation curves. GS, however, decelerated HERG current deactivation in a concentration-dependent manner, which was more noticeable with panaxitriol (PT) than panaxidiol (PD). Consistently, ginseng saponins increased the HERG deactivation time constants with the order of potency of Rg 1 (a major component of PT)>Rf 1 >Rb 1 (a major component of PD). Re had little effect on HERG deactivation. During a cardiac action potential, GS increased the outward HERG current. Conclusion: Ginseng saponins enhance HERG currents, which could be in part a possible mechanism of the shortening cardiac action potential of ginseng saponins.

Aim: To characterize the effects of papaverine on HERG channels expressed in Xenopus oocytes as well as cardiac action potential in rabbit ventricular myocytes. Methods: Conventional microelectrodes were used to record action potential in rabbit ventricular myocytes. HERG currents were recorded by 2-electrode voltage clamp technique in Xenopus oocytes injected with HERG cRNA. Results: Papaverine increased the cardiac action potential duration in rabbit ventricular myocytes. It blocked heterologously-expressed HERG currents in a concentration-dependent manner (IC 50 71.03±4.75 µmol/L, NH 0.80, n=6), whereas another phosphodiesterase inhibitor, theophylline (500 µmol/L), did not. The blockade of papaverine on HERG currents was not voltage-dependent. The slope conductance measured as a slope of the fully activated HERG current-voltage curves decreased from 78.03±4.25 µS of the control to 56.84±5.33, 36.06±6.53, and 27.09±5.50 µS (n=4) by 30, 100, and 300 µmol/L of papaverine, respectively. Papaverine (100 µmol/L) caused a 9 mV hyperpolarizing shift in the voltage-dependence of steady-state inactivation, but there were no changes in the voltage-dependence of HERG current activation. Papaverine blocked HERG channels in the closed, open, and inactivated states. Conclusion: These results showed that papaverine blocked HERG channels in a voltage-and state-independent manner, which may most likely be the major mechanism of papaverine-induced cardiac arrhythmia reported in humans.

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