Channelpedia

PubMed 19336893


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.4



Title: The effects of ginsenoside Rg(3) on human Kv1.4 channel currents without the N-terminal rapid inactivation domain.

Authors: Jun-Ho Lee, Sun-Hye Choi, Byung-Hwan Lee, Tae-Joon Shin, Mi Kyung Pyo, Sung-Hee Hwang, Bo-Ra Kim, Sang-Mok Lee, Dong-Ho Bae, Hyewhon Rhim, Seung-Yeol Nah

Journal, date & volume: Biol. Pharm. Bull., 2009 Apr , 32, 614-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19336893


Abstract
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 hKv1.4Delta2-61 channels by N-terminal deletion of 2-61 amino acid residues. We investigated the effect of Rg(3) on hKv1.4Delta2-61 channel currents. We found that Rg(3) preferentially inhibited non-inactivating outward currents rather than peak outward currents of hKv1.4Delta2-61 channels. The mutation of K531 hKv1.4Delta2-61 to K531Y hKv1.4Delta2-61 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 hKv1.4Delta2-61 channels.