FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3020087722> ?p ?o ?g. }

• W3020087722 endingPage "106" @default.
• W3020087722 startingPage "96" @default.
• W3020087722 abstract "Abstract In ventricular myocytes, stimulation of β-adrenergic receptors activates critical cardiac signaling pathways, leading to shorter action potentials and increased contraction strength during the “fight-or-flight” response. These changes primarily result, at the cellular level, from the coordinated phosphorylation of multiple targets by protein kinase A. Although mathematical models of the intracellular signaling downstream of β-adrenergic receptor activation have previously been described, only a limited number of studies have explored quantitative interactions between intracellular signaling and electrophysiology in human ventricular myocytes. Accordingly, our objective was to develop an integrative mathematical model of β-adrenergic receptor signaling, electrophysiology, and intracellular calcium (Ca2+) handling in the healthy human ventricular myocyte. We combined published mathematical models of intracellular signaling and electrophysiology, then calibrated the model results against voltage clamp data and physiological changes occurring after stimulation of β-adrenergic receptors with isoproterenol. We subsequently: (1) explored how molecular variability in different categories of model parameters translated into phenotypic variability; (2) identified the most important parameters determining physiological cellular outputs in the model before and after β-adrenergic receptor stimulation; and (3) investigated which molecular level alterations can produce a phenotype indicative of heart failure with preserved ejection fraction (HFpEF). Major results included: (1) variability in parameters that controlled intracellular signaling caused qualitatively different behavior than variability in parameters controlling ion transport pathways; (2) the most important model parameters determining action potential duration and intracellular Ca2+ transient amplitude were generally consistent before and after β-adrenergic receptor stimulation, except for a shift in the importance of K+ currents in determining action potential duration; and (3) decreased Ca2+ uptake into the sarcoplasmic reticulum, increased Ca2+ extrusion through Na+/Ca2+ exchanger and decreased Ca2+ leak from the sarcoplasmic reticulum may contribute to HFpEF. Overall, this study provided novel insight into the phenotypic consequences of molecular variability, and our integrated model may be useful in the design and interpretation of future experimental studies of interactions between β-adrenergic signaling and cellular physiology in human ventricular myocytes." @default.
• W3020087722 created "2020-05-01" @default.
• W3020087722 creator A5000485841 @default.
• W3020087722 creator A5015687477 @default.
• W3020087722 creator A5015952152 @default.
• W3020087722 creator A5019600201 @default.
• W3020087722 creator A5089176992 @default.
• W3020087722 date "2020-06-01" @default.
• W3020087722 modified "2023-09-25" @default.
• W3020087722 title "Quantitative analysis of variability in an integrated model of human ventricular electrophysiology and β-adrenergic signaling" @default.
• W3020087722 cites W1018973536 @default.
• W3020087722 cites W1492161308 @default.
• W3020087722 cites W1502330209 @default.
• W3020087722 cites W1965139977 @default.
• W3020087722 cites W1974994056 @default.
• W3020087722 cites W1975641338 @default.
• W3020087722 cites W1980258822 @default.
• W3020087722 cites W1986061022 @default.
• W3020087722 cites W1989943515 @default.
• W3020087722 cites W1994147843 @default.
• W3020087722 cites W2023201524 @default.
• W3020087722 cites W2023220066 @default.
• W3020087722 cites W2027509335 @default.
• W3020087722 cites W2028420847 @default.
• W3020087722 cites W2034944531 @default.
• W3020087722 cites W2038189266 @default.
• W3020087722 cites W2043276871 @default.
• W3020087722 cites W2044024203 @default.
• W3020087722 cites W2047427527 @default.
• W3020087722 cites W2050824263 @default.
• W3020087722 cites W2052580196 @default.
• W3020087722 cites W2057547167 @default.
• W3020087722 cites W2075402097 @default.
• W3020087722 cites W2076548466 @default.
• W3020087722 cites W2078403132 @default.
• W3020087722 cites W2079329400 @default.
• W3020087722 cites W2081895934 @default.
• W3020087722 cites W2094992315 @default.
• W3020087722 cites W2097149135 @default.
• W3020087722 cites W2098933235 @default.
• W3020087722 cites W2109637083 @default.
• W3020087722 cites W2113420824 @default.
• W3020087722 cites W2115475608 @default.
• W3020087722 cites W2118406111 @default.
• W3020087722 cites W2140512990 @default.
• W3020087722 cites W2142764185 @default.
• W3020087722 cites W2145563296 @default.
• W3020087722 cites W2152136740 @default.
• W3020087722 cites W2159808944 @default.
• W3020087722 cites W2213703168 @default.
• W3020087722 cites W2304315762 @default.
• W3020087722 cites W2510800797 @default.
• W3020087722 cites W2538021067 @default.
• W3020087722 cites W2606932135 @default.
• W3020087722 cites W2618713948 @default.
• W3020087722 cites W2747733237 @default.
• W3020087722 cites W2762062721 @default.
• W3020087722 cites W2767380796 @default.
• W3020087722 cites W2809984714 @default.
• W3020087722 cites W2831922643 @default.
• W3020087722 cites W2884120920 @default.
• W3020087722 cites W2901982716 @default.
• W3020087722 cites W2908142868 @default.
• W3020087722 cites W2921336580 @default.
• W3020087722 cites W2949599838 @default.
• W3020087722 cites W2951315938 @default.
• W3020087722 cites W2953377360 @default.
• W3020087722 cites W2953513972 @default.
• W3020087722 doi "https://doi.org/10.1016/j.yjmcc.2020.04.009" @default.
• W3020087722 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7944586" @default.
• W3020087722 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32330487" @default.
• W3020087722 hasPublicationYear "2020" @default.
• W3020087722 type Work @default.
• W3020087722 sameAs 3020087722 @default.
• W3020087722 citedByCount "16" @default.
• W3020087722 countsByYear W30200877222020 @default.
• W3020087722 countsByYear W30200877222021 @default.
• W3020087722 countsByYear W30200877222022 @default.
• W3020087722 countsByYear W30200877222023 @default.
• W3020087722 crossrefType "journal-article" @default.
• W3020087722 hasAuthorship W3020087722A5000485841 @default.
• W3020087722 hasAuthorship W3020087722A5015687477 @default.
• W3020087722 hasAuthorship W3020087722A5015952152 @default.
• W3020087722 hasAuthorship W3020087722A5019600201 @default.
• W3020087722 hasAuthorship W3020087722A5089176992 @default.
• W3020087722 hasBestOaLocation W30200877222 @default.
• W3020087722 hasConcept C126322002 @default.
• W3020087722 hasConcept C158453852 @default.
• W3020087722 hasConcept C169760540 @default.
• W3020087722 hasConcept C170493617 @default.
• W3020087722 hasConcept C185263204 @default.
• W3020087722 hasConcept C71924100 @default.
• W3020087722 hasConcept C86803240 @default.
• W3020087722 hasConceptScore W3020087722C126322002 @default.
• W3020087722 hasConceptScore W3020087722C158453852 @default.
• W3020087722 hasConceptScore W3020087722C169760540 @default.
• W3020087722 hasConceptScore W3020087722C170493617 @default.
• W3020087722 hasConceptScore W3020087722C185263204 @default.

• next