FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3033404513> ?p ?o ?g. }

• W3033404513 endingPage "376" @default.
• W3033404513 startingPage "364" @default.
• W3033404513 abstract "Background Until recently, the mechanism for the malignant hyperthermia crisis has been attributed solely to sustained massive Ca2+ release from the sarcoplasmic reticulum on exposure to triggering agents. This study tested the hypothesis that transient receptor potential cation (TRPC) channels are important contributors to the Ca2+ dyshomeostasis in a mouse model relevant to malignant hyperthermia. Methods This study examined the mechanisms responsible for Ca2+ dyshomeostasis in RYR1-p.G2435R mouse muscles and muscle cells using calcium and sodium ion selective microelectrodes, manganese quench of Fura2 fluorescence, and Western blots. Results RYR1-p.G2435R mouse muscle cells have chronically elevated intracellular resting calcium and sodium and rate of manganese quench (homozygous greater than heterozygous) compared with wild-type muscles. After exposure to 1-oleoyl-2-acetyl-sn-glycerol, a TRPC3/6 activator, increases in intracellular resting calcium/sodium were significantly greater in RYR1-p.G2435R muscles (from 153 ± 11 nM/10 ± 0.5 mM to 304 ± 45 nM/14.2 ± 0.7 mM in heterozygotes P &lt; 0.001] and from 251 ± 25 nM/13.9 ± 0.5 mM to 534 ± 64 nM/20.9 ± 1.5 mM in homozygotes [P &lt; 0.001] compared with 123 ± 3 nM/8 ± 0.1 mM to 196 ± 27 nM/9.4 ± 0.7 mM in wild type). These increases were inhibited both by simply removing extracellular Ca2+ and by exposure to either a nonspecific (gadolinium) or a newly available, more specific pharmacologic agent (SAR7334) to block TRPC6- and TRPC3-mediated cation influx into cells. Furthermore, local pretreatment with SAR7334 partially decreased the elevation of intracellular resting calcium that is seen in RYR1-p.G2435R muscles during exposure to halothane. Western blot analysis showed that expression of TRPC3 and TRPC6 were significantly increased in RYR1-p.G2435R muscles in a gene–dose–dependent manner, supporting their being a primary molecular basis for increased sarcolemmal cation influx. Conclusions Muscle cells in knock-in mice expressing the RYR1-p.G2435R mutation are hypersensitive to TRPC3/6 activators. This hypersensitivity can be negated with pharmacologic agents that block TRPC3/6 activity. This reinforces the working hypothesis that transient receptor potential cation channels play a critical role in causing intracellular calcium and sodium overload in malignant hyperthermia–susceptible muscle, both at rest and during the malignant hyperthermia crisis. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New" @default.
• W3033404513 created "2020-06-12" @default.
• W3033404513 creator A5010930479 @default.
• W3033404513 creator A5013306631 @default.
• W3033404513 creator A5013324757 @default.
• W3033404513 creator A5014793389 @default.
• W3033404513 creator A5045699821 @default.
• W3033404513 creator A5080596515 @default.
• W3033404513 creator A5082456279 @default.
• W3033404513 date "2020-06-05" @default.
• W3033404513 modified "2023-10-06" @default.
• W3033404513 title "Transient Receptor Potential Cation Channels and Calcium Dyshomeostasis in a Mouse Model Relevant to Malignant Hyperthermia" @default.
• W3033404513 cites W1592288818 @default.
• W3033404513 cites W1930588275 @default.
• W3033404513 cites W1963480642 @default.
• W3033404513 cites W1967440360 @default.
• W3033404513 cites W1967785580 @default.
• W3033404513 cites W1977565611 @default.
• W3033404513 cites W1978547646 @default.
• W3033404513 cites W1982717927 @default.
• W3033404513 cites W2000931006 @default.
• W3033404513 cites W2001115224 @default.
• W3033404513 cites W2003484334 @default.
• W3033404513 cites W2011925231 @default.
• W3033404513 cites W2012528202 @default.
• W3033404513 cites W2022880927 @default.
• W3033404513 cites W2027719953 @default.
• W3033404513 cites W2045954062 @default.
• W3033404513 cites W2055837976 @default.
• W3033404513 cites W2056886498 @default.
• W3033404513 cites W2058324461 @default.
• W3033404513 cites W2065663971 @default.
• W3033404513 cites W2087510546 @default.
• W3033404513 cites W2092605434 @default.
• W3033404513 cites W2102204826 @default.
• W3033404513 cites W2106312528 @default.
• W3033404513 cites W2121481190 @default.
• W3033404513 cites W2130024981 @default.
• W3033404513 cites W2131119268 @default.
• W3033404513 cites W2147493307 @default.
• W3033404513 cites W2163073874 @default.
• W3033404513 cites W2301131921 @default.
• W3033404513 cites W2409160137 @default.
• W3033404513 cites W2411885572 @default.
• W3033404513 cites W2886540913 @default.
• W3033404513 cites W2886544522 @default.
• W3033404513 doi "https://doi.org/10.1097/aln.0000000000003387" @default.
• W3033404513 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7367496" @default.
• W3033404513 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33377952" @default.
• W3033404513 hasPublicationYear "2020" @default.
• W3033404513 type Work @default.
• W3033404513 sameAs 3033404513 @default.
• W3033404513 citedByCount "13" @default.
• W3033404513 countsByYear W30334045132020 @default.
• W3033404513 countsByYear W30334045132021 @default.
• W3033404513 countsByYear W30334045132022 @default.
• W3033404513 countsByYear W30334045132023 @default.
• W3033404513 crossrefType "journal-article" @default.
• W3033404513 hasAuthorship W3033404513A5010930479 @default.
• W3033404513 hasAuthorship W3033404513A5013306631 @default.
• W3033404513 hasAuthorship W3033404513A5013324757 @default.
• W3033404513 hasAuthorship W3033404513A5014793389 @default.
• W3033404513 hasAuthorship W3033404513A5045699821 @default.
• W3033404513 hasAuthorship W3033404513A5080596515 @default.
• W3033404513 hasAuthorship W3033404513A5082456279 @default.
• W3033404513 hasBestOaLocation W30334045131 @default.
• W3033404513 hasConcept C113217602 @default.
• W3033404513 hasConcept C12554922 @default.
• W3033404513 hasConcept C126322002 @default.
• W3033404513 hasConcept C134018914 @default.
• W3033404513 hasConcept C155164980 @default.
• W3033404513 hasConcept C170488646 @default.
• W3033404513 hasConcept C170493617 @default.
• W3033404513 hasConcept C181080969 @default.
• W3033404513 hasConcept C181199279 @default.
• W3033404513 hasConcept C185592680 @default.
• W3033404513 hasConcept C2776333580 @default.
• W3033404513 hasConcept C2778470358 @default.
• W3033404513 hasConcept C2779949491 @default.
• W3033404513 hasConcept C2780383360 @default.
• W3033404513 hasConcept C28406088 @default.
• W3033404513 hasConcept C519063684 @default.
• W3033404513 hasConcept C55493867 @default.
• W3033404513 hasConcept C71924100 @default.
• W3033404513 hasConcept C79879829 @default.
• W3033404513 hasConcept C86803240 @default.
• W3033404513 hasConcept C98539663 @default.
• W3033404513 hasConceptScore W3033404513C113217602 @default.
• W3033404513 hasConceptScore W3033404513C12554922 @default.
• W3033404513 hasConceptScore W3033404513C126322002 @default.
• W3033404513 hasConceptScore W3033404513C134018914 @default.
• W3033404513 hasConceptScore W3033404513C155164980 @default.
• W3033404513 hasConceptScore W3033404513C170488646 @default.
• W3033404513 hasConceptScore W3033404513C170493617 @default.
• W3033404513 hasConceptScore W3033404513C181080969 @default.
• W3033404513 hasConceptScore W3033404513C181199279 @default.
• W3033404513 hasConceptScore W3033404513C185592680 @default.
• W3033404513 hasConceptScore W3033404513C2776333580 @default.

• next