Inhibition of the human ether-a-go-go-related gene (HERG) K+ channels by Lindera erythrocarpa.
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 H(2)O fraction of Lindera erythrocarpa were added to the perfusate, both I(HERG) and I(tail) were suppressed, while the hexane fraction, CHCl(3) 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 H(2)O fraction shifted significantly. The BuOH fraction and H(2)O fraction (100 microg/mL) decreased g(max) by 59.6% and 52.9%, respectively. The H(2)O 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.
Hong
Hee-Kyung
HK
Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University College of Medicine, Chuncheon, Korea.
Yoon
Weon-Jong
WJ
Kim
Young Ho
YH
Yoo
Eun-Sook
ES
Jo
Su-Hyun
SH
D000818:Animals; D000440:Butanols / Q000737:chemistry / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D027443:Lindera / Q000737:chemistry*; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000378:metabolism*; D014982:Xenopus laevis
D000440:Butanols; D051638:Ether-A-Go-Go Potassium Channels; D010936:Plant Extracts; D026902:Potassium Channel Blockers