Inhibitory effects of a bisbenzylisoquinline alkaloid dauricine on HERG potassium channels.

BACKGROUND

The roots of Menispermum dauricum have been widely used for the treatment of inflammation, allergy and arrhythmia in China for a long time. Dauricine (Dau), a bisbenzylisoquinline alkaloid from Menispermum dauricum, mainly contributes to the anti-arrhythmic effect and has received pharmacological attention. Dau can prolong the action potential duration (APD), which has been attributed to its ability to modulate Ca(2+) and several K(+) channels. However, its effects on human-ether-a-go-go-related gene (HERG) channels are unknown.

OBJECTIVE

The effects of Dau on HERG channels were investigated.

METHODS

Whole-cell patch-clamp technique was used to record HERG current (I(HERG)) carried by recombinant HERG channels expressed in HEK293 cells.

RESULTS

Dau inhibited I(HERG) in a concentration-dependent manner with an IC(50) of 3.5 μM. Development of block and washout were fast. The inhibitory action of Dau was contingent on channel gating, showing significant voltage and time dependence. Dau inhibited I(HERG) in the open and inactivated states, but not in the closed states. The activation curve was shifted in a negative direction.

CONCLUSIONS

Dau inhibits HERG encoded potassium channels and this action might be a molecular mechanism for the previously reported APD prolongation with this drug.