FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2162445663> ?p ?o ?g. }

• W2162445663 endingPage "966" @default.
• W2162445663 startingPage "960" @default.
• W2162445663 abstract "Background Atrial fibrillation is the most common sustained cardiac arrhythmia in adults. We hypothesized that gain-of-function KCNQ1 mutations previously associated with familial atrial fibrillation have distinct pharmacological properties that may enable targeted inhibition. Methods and Results Wild-type (WT) KCNQ1 or the familial atrial fibrillation mutation KCNQ1-S140G was heterologously coexpressed with KCNE1 to enable electrophysiological recording of the slow delayed rectifier current ( I Ks ) and investigation of pharmacological effects of the I Ks selective blocker HMR-1556. Coexpression of KCNQ1-S140G with KCNE1 generated potassium currents (S140G- I Ks ) that exhibited greater sensitivity to HMR-1556 than WT- I Ks . Enhanced HMR-1556 sensitivity was also observed for another gain-of-function atrial fibrillation mutation, KCNQ1-V141M. Heteromeric expression of KCNE1 with both KCNQ1-WT and KCNQ1-S140G generated currents (HET- I Ks ) with gain-of-function features, including larger amplitude, a constitutively active component, hyperpolarized voltage dependence of activation, and extremely slow deactivation. A low concentration of HMR-1556, which had little effect on WT- I Ks but was capable of inhibiting the mutant channel, reduced both instantaneous and steady state HET- I Ks to levels that were not significantly different from WT- I Ks and attenuated use-dependent accumulation of the current. In cultured adult rabbit left atrial myocytes, expression of S140G- I Ks shortened action potential duration compared with WT- I Ks . Application of HMR-1556 mitigated S140G- I Ks –induced action potential duration shortening and did not alter action potential duration in cells expressing WT- I Ks . Conclusions The enhanced sensitivity of KCNQ1 gain-of-function mutations for HMR-1556 suggests the possibility of selective therapeutic targeting, and, therefore, our data illustrate a potential proof of principle for genotype-specific treatment of this heritable arrhythmia." @default.
• W2162445663 created "2016-06-24" @default.
• W2162445663 creator A5013560175 @default.
• W2162445663 creator A5025221527 @default.
• W2162445663 creator A5030984711 @default.
• W2162445663 creator A5045992434 @default.
• W2162445663 creator A5057426360 @default.
• W2162445663 creator A5077586460 @default.
• W2162445663 creator A5083477734 @default.
• W2162445663 date "2013-10-01" @default.
• W2162445663 modified "2023-10-18" @default.
• W2162445663 title "Selective Targeting of Gain-of-Function KCNQ1 Mutations Predisposing to Atrial Fibrillation" @default.
• W2162445663 cites W1534615920 @default.
• W2162445663 cites W1594345270 @default.
• W2162445663 cites W1980935281 @default.
• W2162445663 cites W1981468825 @default.
• W2162445663 cites W1986890860 @default.
• W2162445663 cites W1988911499 @default.
• W2162445663 cites W1991752378 @default.
• W2162445663 cites W1999765072 @default.
• W2162445663 cites W2003039702 @default.
• W2162445663 cites W2018216317 @default.
• W2162445663 cites W2020500996 @default.
• W2162445663 cites W2021591607 @default.
• W2162445663 cites W2022414157 @default.
• W2162445663 cites W2025470533 @default.
• W2162445663 cites W2036174086 @default.
• W2162445663 cites W2037988353 @default.
• W2162445663 cites W2038042463 @default.
• W2162445663 cites W2044779639 @default.
• W2162445663 cites W2050856345 @default.
• W2162445663 cites W2053535889 @default.
• W2162445663 cites W2055928084 @default.
• W2162445663 cites W2057767278 @default.
• W2162445663 cites W2065958606 @default.
• W2162445663 cites W2066861842 @default.
• W2162445663 cites W2082442751 @default.
• W2162445663 cites W2093033692 @default.
• W2162445663 cites W2095862415 @default.
• W2162445663 cites W2098192568 @default.
• W2162445663 cites W2117216522 @default.
• W2162445663 cites W2123262667 @default.
• W2162445663 cites W2126590887 @default.
• W2162445663 cites W2140868856 @default.
• W2162445663 cites W2151074096 @default.
• W2162445663 cites W2152124063 @default.
• W2162445663 cites W2154122229 @default.
• W2162445663 cites W2155779925 @default.
• W2162445663 cites W2340349481 @default.
• W2162445663 cites W4292022394 @default.
• W2162445663 doi "https://doi.org/10.1161/circep.113.000439" @default.
• W2162445663 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3892565" @default.
• W2162445663 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24006450" @default.
• W2162445663 hasPublicationYear "2013" @default.
• W2162445663 type Work @default.
• W2162445663 sameAs 2162445663 @default.
• W2162445663 citedByCount "30" @default.
• W2162445663 countsByYear W21624456632014 @default.
• W2162445663 countsByYear W21624456632015 @default.
• W2162445663 countsByYear W21624456632016 @default.
• W2162445663 countsByYear W21624456632017 @default.
• W2162445663 countsByYear W21624456632018 @default.
• W2162445663 countsByYear W21624456632019 @default.
• W2162445663 countsByYear W21624456632020 @default.
• W2162445663 countsByYear W21624456632021 @default.
• W2162445663 countsByYear W21624456632022 @default.
• W2162445663 countsByYear W21624456632023 @default.
• W2162445663 crossrefType "journal-article" @default.
• W2162445663 hasAuthorship W2162445663A5013560175 @default.
• W2162445663 hasAuthorship W2162445663A5025221527 @default.
• W2162445663 hasAuthorship W2162445663A5030984711 @default.
• W2162445663 hasAuthorship W2162445663A5045992434 @default.
• W2162445663 hasAuthorship W2162445663A5057426360 @default.
• W2162445663 hasAuthorship W2162445663A5077586460 @default.
• W2162445663 hasAuthorship W2162445663A5083477734 @default.
• W2162445663 hasBestOaLocation W21624456631 @default.
• W2162445663 hasConcept C104317684 @default.
• W2162445663 hasConcept C126322002 @default.
• W2162445663 hasConcept C134018914 @default.
• W2162445663 hasConcept C143065580 @default.
• W2162445663 hasConcept C147944092 @default.
• W2162445663 hasConcept C164705383 @default.
• W2162445663 hasConcept C185263204 @default.
• W2162445663 hasConcept C185592680 @default.
• W2162445663 hasConcept C2777356233 @default.
• W2162445663 hasConcept C2779161974 @default.
• W2162445663 hasConcept C3020204279 @default.
• W2162445663 hasConcept C501734568 @default.
• W2162445663 hasConcept C54355233 @default.
• W2162445663 hasConcept C71924100 @default.
• W2162445663 hasConcept C83743174 @default.
• W2162445663 hasConcept C86803240 @default.
• W2162445663 hasConceptScore W2162445663C104317684 @default.
• W2162445663 hasConceptScore W2162445663C126322002 @default.
• W2162445663 hasConceptScore W2162445663C134018914 @default.
• W2162445663 hasConceptScore W2162445663C143065580 @default.
• W2162445663 hasConceptScore W2162445663C147944092 @default.
• W2162445663 hasConceptScore W2162445663C164705383 @default.

• next