Matches in SemOpenAlex for { <https://semopenalex.org/work/W2004235735> ?p ?o ?g. }
Showing items 1 to 87 of
87
with 100 items per page.
- W2004235735 endingPage "415a" @default.
- W2004235735 startingPage "415a" @default.
- W2004235735 abstract "A channelopathic Leu433Pro (L433P) mutation in the cardiac ryanodine receptor (RyR2) alters intracellular Ca2+ handling and is associated with malignant arrhythmia. This mutation is reported to exclusively co-inherit with a common single nucleotide polymorphism (SNP) Gly1885Glu (G1885E) present on the same allele (i.e. in cis). We investigated the functional impact of the G1885E SNP on L433P channels. RyR2-null HEK cells were used as the background for the systematic expression of homo- and heteromeric RyR2 channels composed of recombinant wild-type (WT) subunits, and those containing L433P and G1885E substitutions. Homomeric G1885E channels were functionally normal, but Ca2+ handling abnormalities associated with the L433P mutation were exacerbated by complementation with the G1885E in cis. At the cellular level, channel dysfunction manifested as reduced caffeine-evoked Ca2+ release and decreased ER Ca2+ store content. These findings suggest that although L433P is not a typical gain-of-function mutation it augments basal channel activity. Co-expression of L433P subunits with those containing G1885E (i.e. in trans complementation) attenuated L433P mutant channel dysfunction. Cells expressing heteromeric assemblies of L433P and G1885E subunits exhibited caffeine-activation profiles, homeostatic and post-activation Ca2+ fluxes and ER Ca2+ loads that were comparable to those typical of WT channels. Our data show that the genotype, allelic distribution and the resultant mode of L433P and G1885E channel assembly (i.e. cis or trans subunit complementation) has divergent effects on RyR2 channel (dys)function. The G1885E SNP may be a complex determinant of channel behaviour in situ and the potential therapeutic benefits of normalising mutant channel dysfunction via trans-complementation strategies should be further explored." @default.
- W2004235735 created "2016-06-24" @default.
- W2004235735 creator A5017275427 @default.
- W2004235735 creator A5019190399 @default.
- W2004235735 creator A5031461490 @default.
- W2004235735 creator A5040077633 @default.
- W2004235735 creator A5046935369 @default.
- W2004235735 creator A5066937591 @default.
- W2004235735 date "2011-02-01" @default.
- W2004235735 modified "2023-09-27" @default.
- W2004235735 title "Trans Complementation with the Common G1885E Polymorphism Attenuates Mutant RyR2 L433P Channel Dysfunction" @default.
- W2004235735 doi "https://doi.org/10.1016/j.bpj.2010.12.2457" @default.
- W2004235735 hasPublicationYear "2011" @default.
- W2004235735 type Work @default.
- W2004235735 sameAs 2004235735 @default.
- W2004235735 citedByCount "0" @default.
- W2004235735 crossrefType "journal-article" @default.
- W2004235735 hasAuthorship W2004235735A5017275427 @default.
- W2004235735 hasAuthorship W2004235735A5019190399 @default.
- W2004235735 hasAuthorship W2004235735A5031461490 @default.
- W2004235735 hasAuthorship W2004235735A5040077633 @default.
- W2004235735 hasAuthorship W2004235735A5046935369 @default.
- W2004235735 hasAuthorship W2004235735A5066937591 @default.
- W2004235735 hasBestOaLocation W20042357351 @default.
- W2004235735 hasConcept C104292427 @default.
- W2004235735 hasConcept C104317684 @default.
- W2004235735 hasConcept C113217602 @default.
- W2004235735 hasConcept C135763542 @default.
- W2004235735 hasConcept C139275648 @default.
- W2004235735 hasConcept C143065580 @default.
- W2004235735 hasConcept C153209595 @default.
- W2004235735 hasConcept C153911025 @default.
- W2004235735 hasConcept C170493617 @default.
- W2004235735 hasConcept C174510640 @default.
- W2004235735 hasConcept C180754005 @default.
- W2004235735 hasConcept C185592680 @default.
- W2004235735 hasConcept C188082640 @default.
- W2004235735 hasConcept C190712762 @default.
- W2004235735 hasConcept C207583985 @default.
- W2004235735 hasConcept C2776104367 @default.
- W2004235735 hasConcept C501734568 @default.
- W2004235735 hasConcept C54355233 @default.
- W2004235735 hasConcept C79879829 @default.
- W2004235735 hasConcept C86803240 @default.
- W2004235735 hasConcept C95444343 @default.
- W2004235735 hasConceptScore W2004235735C104292427 @default.
- W2004235735 hasConceptScore W2004235735C104317684 @default.
- W2004235735 hasConceptScore W2004235735C113217602 @default.
- W2004235735 hasConceptScore W2004235735C135763542 @default.
- W2004235735 hasConceptScore W2004235735C139275648 @default.
- W2004235735 hasConceptScore W2004235735C143065580 @default.
- W2004235735 hasConceptScore W2004235735C153209595 @default.
- W2004235735 hasConceptScore W2004235735C153911025 @default.
- W2004235735 hasConceptScore W2004235735C170493617 @default.
- W2004235735 hasConceptScore W2004235735C174510640 @default.
- W2004235735 hasConceptScore W2004235735C180754005 @default.
- W2004235735 hasConceptScore W2004235735C185592680 @default.
- W2004235735 hasConceptScore W2004235735C188082640 @default.
- W2004235735 hasConceptScore W2004235735C190712762 @default.
- W2004235735 hasConceptScore W2004235735C207583985 @default.
- W2004235735 hasConceptScore W2004235735C2776104367 @default.
- W2004235735 hasConceptScore W2004235735C501734568 @default.
- W2004235735 hasConceptScore W2004235735C54355233 @default.
- W2004235735 hasConceptScore W2004235735C79879829 @default.
- W2004235735 hasConceptScore W2004235735C86803240 @default.
- W2004235735 hasConceptScore W2004235735C95444343 @default.
- W2004235735 hasIssue "3" @default.
- W2004235735 hasLocation W20042357351 @default.
- W2004235735 hasOpenAccess W2004235735 @default.
- W2004235735 hasPrimaryLocation W20042357351 @default.
- W2004235735 hasRelatedWork W1518010816 @default.
- W2004235735 hasRelatedWork W1935916792 @default.
- W2004235735 hasRelatedWork W1968505518 @default.
- W2004235735 hasRelatedWork W1974402175 @default.
- W2004235735 hasRelatedWork W2004235735 @default.
- W2004235735 hasRelatedWork W2009647017 @default.
- W2004235735 hasRelatedWork W2028502345 @default.
- W2004235735 hasRelatedWork W2091920404 @default.
- W2004235735 hasRelatedWork W2176206542 @default.
- W2004235735 hasRelatedWork W2759340633 @default.
- W2004235735 hasVolume "100" @default.
- W2004235735 isParatext "false" @default.
- W2004235735 isRetracted "false" @default.
- W2004235735 magId "2004235735" @default.
- W2004235735 workType "article" @default.