Linked Life Data

17959711

Source:http://linkedlifedata.com/resource/pubmed/id/17959711

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-2-22
pubmed:abstractText
We have demonstrated previously that the 20(S) but not the 20(R) form of ginsenoside Rg(3) inhibited K(+) currents flowing through Kv1.4 (hKv1.4) channels expressed in Xenopus laevis oocytes, pointing to the presence of specific interaction site(s) for Rg(3) in the hKv1.4 channel. In the current study, we sought to identify this site(s). To this end, we first assessed how point mutations of various amino acid residues of the hKv1.4 channel affected inhibition by 20(S)-ginsenoside Rg(3) (Rg(3)). Lys531 residue is known to be a key site for K(+) activation and to be part of the extracellular tetraethylammonium (TEA) binding site; the mutation K531Y abolished the Rg(3) effect and made the Kv1.4 channel sensitive to TEA applied to the extracellular side of the membrane. Mutations of many other residues, including the pH sensitive-site (H507Q), were without any significant effect. We next examined whether K(+) and TEA could alter the effect of Rg(3) and vice versa. We found that 1) raising [K(+)](o) reduced the inhibitory effect of Rg(3) on hKv1.4 channel currents, whereas Rg(3) shifted the K(+) activation curve to the right, and 2) TEA caused a rightward shift of the Rg(3) concentration-response curve of wild-type hKv1.4 channel currents, whereas Rg(3) caused a rightward shift of the TEA concentration-response curve of K531Y mutant channel currents. The docked modeling revealed that Lys531 plays a key role in forming hydrogen bonds between Rg(3) and hKv1.4 channels. These results indicate that Rg(3) inhibits the hKv1.4 channel current by interacting with residue Lys531.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
619-26
pubmed:meshHeading
pubmed-meshheading:17959711-Amino Acid Substitution, pubmed-meshheading:17959711-Animals, pubmed-meshheading:17959711-Binding Sites, pubmed-meshheading:17959711-Dose-Response Relationship, Drug, pubmed-meshheading:17959711-Female, pubmed-meshheading:17959711-Ginsenosides, pubmed-meshheading:17959711-Humans, pubmed-meshheading:17959711-Hydrogen Bonding, pubmed-meshheading:17959711-Inhibitory Concentration 50, pubmed-meshheading:17959711-Kv1.4 Potassium Channel, pubmed-meshheading:17959711-Lysine, pubmed-meshheading:17959711-Models, Molecular, pubmed-meshheading:17959711-Molecular Structure, pubmed-meshheading:17959711-Oocytes, pubmed-meshheading:17959711-Patch-Clamp Techniques, pubmed-meshheading:17959711-Potassium Channel Blockers, pubmed-meshheading:17959711-Protein Binding, pubmed-meshheading:17959711-Tetraethylammonium, pubmed-meshheading:17959711-Xenopus laevis
pubmed:year
2008
pubmed:articleTitle
Ginsenoside Rg3 inhibits human Kv1.4 channel currents by interacting with the Lys531 residue.
pubmed:affiliation
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701 Korea.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't