Matches in SemOpenAlex for { <https://semopenalex.org/work/W2583823452> ?p ?o ?g. }
Showing items 1 to 84 of
84
with 100 items per page.
- W2583823452 abstract "The naturally occurring resin acid dehydroabietic acid (DHAA) opens a voltage-gated K channel by shifting the voltage dependence of the channel activation to more negative voltages. We synthesized 140 DHAA-derivatives and found that subtle alterations in the chemical structure of DHAA can have a large effect on the channel opening. Several of the channel-opening DHAA derivatives reduced excitability in dorsal root ganglion neurons, suggesting a possibility to act against diseases with increased cellular excitability. Here we searched for the mechanism and site of action for the DHAA derivatives. We expressed the non-inactivating Shaker K channel in Xenopus oocytes and studied the ion currents with a two-electrode voltage clamp technique. By utilizing the ILT-mutant, which separates the final channel-opening transition from the earlier transitions, we found that the DHAA derivatives had an almost isolated effect on the channel-opening transition. 100 μM of one DHAA derivative affected this last transition by −65 mV. We also found that the charge profile of the voltage sensor S4 was critical for the effect. Addition of positively charged arginines in specific positions increased the channel opening effects of the negatively charged DHAA derivatives, while addition of arginines on the opposite side of the S4 helix had opposing effects, suggesting that the DHAA derivatives support or prevent rotation of S4 to support or prevent channel opening. In general, the DHAA derivatives affected channel closing kinetic but not channel opening kinetic suggesting a rather specific effect and site of action. In-silico docking, molecular dynamics, and mutational analyses suggested a binding site in the cleft between the transmembrane segments S3 and S4. We conclude that certain resin-acid derivatives bind at the interface between the lipid bilayer and S3 and S4 of the channel's voltage-sensor domain, to electrostatically facilitate K channel opening." @default.
- W2583823452 created "2017-02-10" @default.
- W2583823452 creator A5008875190 @default.
- W2583823452 creator A5012208856 @default.
- W2583823452 creator A5026276102 @default.
- W2583823452 creator A5040529930 @default.
- W2583823452 creator A5054685745 @default.
- W2583823452 creator A5059848596 @default.
- W2583823452 creator A5077399161 @default.
- W2583823452 date "2017-02-01" @default.
- W2583823452 modified "2023-09-28" @default.
- W2583823452 title "Drug Interaction at the Lipid Bilayer-Potassium Channel Interface" @default.
- W2583823452 doi "https://doi.org/10.1016/j.bpj.2016.11.253" @default.
- W2583823452 hasPublicationYear "2017" @default.
- W2583823452 type Work @default.
- W2583823452 sameAs 2583823452 @default.
- W2583823452 citedByCount "1" @default.
- W2583823452 countsByYear W25838234522018 @default.
- W2583823452 crossrefType "journal-article" @default.
- W2583823452 hasAuthorship W2583823452A5008875190 @default.
- W2583823452 hasAuthorship W2583823452A5012208856 @default.
- W2583823452 hasAuthorship W2583823452A5026276102 @default.
- W2583823452 hasAuthorship W2583823452A5040529930 @default.
- W2583823452 hasAuthorship W2583823452A5054685745 @default.
- W2583823452 hasAuthorship W2583823452A5059848596 @default.
- W2583823452 hasAuthorship W2583823452A5077399161 @default.
- W2583823452 hasBestOaLocation W25838234521 @default.
- W2583823452 hasConcept C100837961 @default.
- W2583823452 hasConcept C12554922 @default.
- W2583823452 hasConcept C170493617 @default.
- W2583823452 hasConcept C178790620 @default.
- W2583823452 hasConcept C181911157 @default.
- W2583823452 hasConcept C185592680 @default.
- W2583823452 hasConcept C39944091 @default.
- W2583823452 hasConcept C41625074 @default.
- W2583823452 hasConcept C50254741 @default.
- W2583823452 hasConcept C50952357 @default.
- W2583823452 hasConcept C537181965 @default.
- W2583823452 hasConcept C55493867 @default.
- W2583823452 hasConcept C71240020 @default.
- W2583823452 hasConcept C83743174 @default.
- W2583823452 hasConcept C86803240 @default.
- W2583823452 hasConceptScore W2583823452C100837961 @default.
- W2583823452 hasConceptScore W2583823452C12554922 @default.
- W2583823452 hasConceptScore W2583823452C170493617 @default.
- W2583823452 hasConceptScore W2583823452C178790620 @default.
- W2583823452 hasConceptScore W2583823452C181911157 @default.
- W2583823452 hasConceptScore W2583823452C185592680 @default.
- W2583823452 hasConceptScore W2583823452C39944091 @default.
- W2583823452 hasConceptScore W2583823452C41625074 @default.
- W2583823452 hasConceptScore W2583823452C50254741 @default.
- W2583823452 hasConceptScore W2583823452C50952357 @default.
- W2583823452 hasConceptScore W2583823452C537181965 @default.
- W2583823452 hasConceptScore W2583823452C55493867 @default.
- W2583823452 hasConceptScore W2583823452C71240020 @default.
- W2583823452 hasConceptScore W2583823452C83743174 @default.
- W2583823452 hasConceptScore W2583823452C86803240 @default.
- W2583823452 hasLocation W25838234521 @default.
- W2583823452 hasOpenAccess W2583823452 @default.
- W2583823452 hasPrimaryLocation W25838234521 @default.
- W2583823452 hasRelatedWork W102549573 @default.
- W2583823452 hasRelatedWork W1967113088 @default.
- W2583823452 hasRelatedWork W1996049812 @default.
- W2583823452 hasRelatedWork W1997464544 @default.
- W2583823452 hasRelatedWork W1998401151 @default.
- W2583823452 hasRelatedWork W2005105608 @default.
- W2583823452 hasRelatedWork W2005584336 @default.
- W2583823452 hasRelatedWork W2011556562 @default.
- W2583823452 hasRelatedWork W2024022389 @default.
- W2583823452 hasRelatedWork W2040807238 @default.
- W2583823452 hasRelatedWork W2056581537 @default.
- W2583823452 hasRelatedWork W2083222737 @default.
- W2583823452 hasRelatedWork W2088553801 @default.
- W2583823452 hasRelatedWork W2089838442 @default.
- W2583823452 hasRelatedWork W2093350639 @default.
- W2583823452 hasRelatedWork W2133509911 @default.
- W2583823452 hasRelatedWork W2154001744 @default.
- W2583823452 hasRelatedWork W2154086558 @default.
- W2583823452 hasRelatedWork W2157696981 @default.
- W2583823452 hasRelatedWork W2163212469 @default.
- W2583823452 isParatext "false" @default.
- W2583823452 isRetracted "false" @default.
- W2583823452 magId "2583823452" @default.
- W2583823452 workType "article" @default.