Inhibition of the Human Ether-a-go-go-related Gene (HERG) K⁺ Channels by Lindera erythrocarpa

초록

Lindera erythrocarpa Makino (Lauraceae) is used as a traditional medicine for analgesic, antidote, and antibacterial purposes and shows anti-tumor activity. We studied the effects of Lindera erythrocarpa on the human ether-a-go-go-related gene (HERG) channel, which appears of importance in favoring cancer progression in vivo and determining cardiac action potential duration. Application of MeOH extract of Lindera erythrocarpa showed a dose-dependent decrease in the amplitudes of the outward currents measured at the end of the pulse (I-HERG) and the tail currents of HERG (I-tail). When the BuOH fraction and H2O fraction of Lindera erythrocarpa were added to the perfusate, both I-HERG and I-tail were suppressed, while the hexane fraction, CHCl3 fraction, and EtOAc fraction did not inhibit either I-HERG or I-tail. The potential required for half-maximal activation caused by EtOAc fraction, BuOH fraction, and H2O fraction shifted significantly. The BuOH fraction and H2O fraction (100 mu g/mL) decreased g(max) by 59.6% and 52.9%, respectively. The H2O fraction-and BuOH fraction-induced blockades of I-tail progressively decreased with increasing depolarization, showing the voltage-dependent block. Our findings suggest that Lindera erythrocarpa, a traditional medicine, blocks HERG channel, which could contribute to its anticancer and cardiac arrhythmogenic effect.

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