The Effects of Ginsenoside Rg_3 on Human Kv1.4 Channel Currents without the N-Terminal Rapid Inactivation Domain(Pharmacology)

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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 Rg_3 (Rg_3), 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 Rg_3 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 Rg_3 on hKv1.4Δ2-61 channel currents. We found that Rg_3 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 Rg_3 inhibitions on non-inactivating outward currents. Rg_3 treatment increased the C-type inactivation rate, but raising the extracellular [K^+]_o reversed Rg_3 action. These results provide additional evidence that K531 residue also plays an important role in the Rg_3-mediated non-inactivating current blockages and in Rg_3-mediated increase of the C-type inactivation rate in hKv1.4Δ2-61 channels.
社団法人日本薬学会の論文
2009-04-01

The Effects of Ginsenoside Rg_3 on Human Kv1.4 Channel Currents without the N-Terminal Rapid Inactivation Domain(Pharmacology)

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