Matches in SemOpenAlex for { <https://semopenalex.org/work/W1988865285> ?p ?o ?g. }
Showing items 1 to 73 of
73
with 100 items per page.
- W1988865285 endingPage "35a" @default.
- W1988865285 startingPage "34a" @default.
- W1988865285 abstract "In human heart, pore-forming KCNQ1 subunits associate with auxiliary KCNE1 subunits to generate the slowly activating, delayed rectifier potassium current, IKs. Decreases in IKs, due to either congenital mutations in KCNQ1/KCNE1 subunits or the adverse neuro-hormonal milieu accompanying heart failure, delay cardiac repolarization, leading to long QT syndrome (LQTS). LQTS predisposes to lethal ventricular arrhythmias and sudden cardiac death. How KCNQ1/KCNE1 channel trafficking in the heart proceeds and is regulated is unknown. However, understanding this process is critical both for fundamental mechanistic insights into LQTS, and for rational development of potential new therapies for this condition. We sought to develop optical tools that permit direct visualization of KCNQ1/KCNE1 subunit assembly and trafficking in heart cells. KCNQ1 and KCNE1 were tagged intra-cellularly with YFP and CFP, respectively, and extra-cellularly with a 13-residue high affinity α-bungarotoxin (BTX) binding site (BBS). The tagged proteins were viable as determined by functional electrophysiological assays in Chinese hamster ovary (CHO) cells– BBS-KCNQ1-YFP expressed alone gave rise to rapidly-activating outward currents, and co-expression with KCNE1-CFP resulted in the slowly activating kinetic signature of IKs. Cell surface BBS-tagged channel subunits were selectively detected with quantum dot. Optical pulse chase assays in human embryonic kidney (HEK 293) cells revealed that surface KCNQ1 channels undergo rapid endocytosis and recycling, and this process is largely unaffected by KCNE1. Tagged KCNQ1/KCNE1 subunits expressed in guinea pig heart cells using adenovirus were targeted to the surface sarcolemma, t-tubules and intercalated disks, similar to endogenous channels. Surprisingly, IKs amplitude remained unchanged with over-expression of either KCNQ1 or KCNE1, suggesting a tightly regulated system for maintaining KCNQ1/KCNE1 surface density." @default.
- W1988865285 created "2016-06-24" @default.
- W1988865285 creator A5027168303 @default.
- W1988865285 creator A5065070785 @default.
- W1988865285 creator A5087032786 @default.
- W1988865285 date "2012-01-01" @default.
- W1988865285 modified "2023-10-16" @default.
- W1988865285 title "Illuminating Trafficking of KCNQ1/KCNE1 Channels in Heart" @default.
- W1988865285 doi "https://doi.org/10.1016/j.bpj.2011.11.216" @default.
- W1988865285 hasPublicationYear "2012" @default.
- W1988865285 type Work @default.
- W1988865285 sameAs 1988865285 @default.
- W1988865285 citedByCount "0" @default.
- W1988865285 crossrefType "journal-article" @default.
- W1988865285 hasAuthorship W1988865285A5027168303 @default.
- W1988865285 hasAuthorship W1988865285A5065070785 @default.
- W1988865285 hasAuthorship W1988865285A5087032786 @default.
- W1988865285 hasBestOaLocation W19888652851 @default.
- W1988865285 hasConcept C102942909 @default.
- W1988865285 hasConcept C104292427 @default.
- W1988865285 hasConcept C104317684 @default.
- W1988865285 hasConcept C12554922 @default.
- W1988865285 hasConcept C146403970 @default.
- W1988865285 hasConcept C155730078 @default.
- W1988865285 hasConcept C169760540 @default.
- W1988865285 hasConcept C170493617 @default.
- W1988865285 hasConcept C174510640 @default.
- W1988865285 hasConcept C175656101 @default.
- W1988865285 hasConcept C185263204 @default.
- W1988865285 hasConcept C185592680 @default.
- W1988865285 hasConcept C207200792 @default.
- W1988865285 hasConcept C54355233 @default.
- W1988865285 hasConcept C83743174 @default.
- W1988865285 hasConcept C86803240 @default.
- W1988865285 hasConcept C95444343 @default.
- W1988865285 hasConceptScore W1988865285C102942909 @default.
- W1988865285 hasConceptScore W1988865285C104292427 @default.
- W1988865285 hasConceptScore W1988865285C104317684 @default.
- W1988865285 hasConceptScore W1988865285C12554922 @default.
- W1988865285 hasConceptScore W1988865285C146403970 @default.
- W1988865285 hasConceptScore W1988865285C155730078 @default.
- W1988865285 hasConceptScore W1988865285C169760540 @default.
- W1988865285 hasConceptScore W1988865285C170493617 @default.
- W1988865285 hasConceptScore W1988865285C174510640 @default.
- W1988865285 hasConceptScore W1988865285C175656101 @default.
- W1988865285 hasConceptScore W1988865285C185263204 @default.
- W1988865285 hasConceptScore W1988865285C185592680 @default.
- W1988865285 hasConceptScore W1988865285C207200792 @default.
- W1988865285 hasConceptScore W1988865285C54355233 @default.
- W1988865285 hasConceptScore W1988865285C83743174 @default.
- W1988865285 hasConceptScore W1988865285C86803240 @default.
- W1988865285 hasConceptScore W1988865285C95444343 @default.
- W1988865285 hasIssue "3" @default.
- W1988865285 hasLocation W19888652851 @default.
- W1988865285 hasOpenAccess W1988865285 @default.
- W1988865285 hasPrimaryLocation W19888652851 @default.
- W1988865285 hasRelatedWork W1988865285 @default.
- W1988865285 hasRelatedWork W2040031849 @default.
- W1988865285 hasRelatedWork W2040102141 @default.
- W1988865285 hasRelatedWork W2083302642 @default.
- W1988865285 hasRelatedWork W2098200000 @default.
- W1988865285 hasRelatedWork W2124929662 @default.
- W1988865285 hasRelatedWork W2153748973 @default.
- W1988865285 hasRelatedWork W2157491435 @default.
- W1988865285 hasRelatedWork W2385556158 @default.
- W1988865285 hasRelatedWork W2791810059 @default.
- W1988865285 hasVolume "102" @default.
- W1988865285 isParatext "false" @default.
- W1988865285 isRetracted "false" @default.
- W1988865285 magId "1988865285" @default.
- W1988865285 workType "article" @default.