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标题：The Effects of Ginsenoside Rg3 on Human Kv1.4 Channel Currents without the N-Terminal Rapid Inactivation Domain
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作者：Jun-Ho Lee ; Sun-Hye Choi ; Byung-Hwan Lee 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：4
页码：614-618
DOI：10.1248/bpb.32.614
出版社：The Pharmaceutical Society of Japan
摘要：Kv1.4 channel belongs to the family of voltage-gated potassium channels that mediate transient and rapidly inactivating A-type currents and N-type inactivation. This N-type inactivation can be removed by the deletion of N-terminal domains, which exhibit non-inactivating currents and C-type inactivation. In our previous report, we demonstrated that 20( S )-ginsenoside Rg₃ (Rg₃), one of the active ingredients of ginseng saponins, inhibits human Kv1.4 (hKv1.4) channel currents through the interaction with amino acids, including Lys (K) residue, which is known as K⁺ activation and the extracellular tetraethylammonium (TEA) binding site. In the present study, we examined the effects of Rg₃ on hKv1.4 channel currents without the N-terminal rapid inactivation domain. We constructed hKv1.4Δ2-61 channels by N-terminal deletion of 2-61 amino acid residues. We investigated the effect of Rg₃ on hKv1.4Δ2-61 channel currents. We found that Rg₃ preferentially inhibited non-inactivating outward currents rather than peak outward currents of hKv1.4Δ2-61 channels. The mutation of K531 hKv1.4Δ2-61 to K531Y hKv1.4Δ2-61 and raising of extracellular [K⁺]_o abolished Rg₃ inhibitions on non-inactivating outward currents. Rg₃ treatment increased the C-type inactivation rate, but raising the extracellular [K⁺]_o reversed Rg₃ action. These results provide additional evidence that K531 residue also plays an important role in the Rg₃-mediated non-inactivating current blockages and in Rg₃-mediated increase of the C-type inactivation rate in hKv1.4Δ2-61 channels.
关键词：Panax ginseng;ginsenoside Rg3;Kv1.4 channel;N-terminal deletion