Matches in SemOpenAlex for { <https://semopenalex.org/work/W2584701554> ?p ?o ?g. }
Showing items 1 to 87 of
87
with 100 items per page.
- W2584701554 abstract "Inherited cardiomyopathies are a common form of heart disease caused by mutations in sarcomeric proteins with beta cardiac myosin being one of the most frequently affected genes. Since the discovery of the first cardiomyopathy associated mutation in beta-cardiac myosin, a major goal has been to correlate the in vitro myosin motor properties with the contractile performance of cardiac muscle. Mutations that cause hypertrophic cardiomyopathy are the most common form of the disease and are often associated with increased isometric force and hyper-contractility. Therefore, the development of drugs designed to decrease isometric force by reducing the duty ratio (the proportion of ATPase cycle time myosin spends bound to actin) has been proposed for the treatment of hypertrophic cardiomyopathy. There is still no consensus about whether hypertrophic mutations in beta-cardiac myosin increase myofilament calcium sensitivity as is commonly found in troponin mutations. We examine the impact of a small molecule drug proposed to decrease duty ratio (para-Nitroblebbistatin) using purified human beta cardiac myosin motor assays and studies of permeabilized human cardiac muscle mechanics. We find that this drug reduces actin-activated ATPase and in vitro motility while not changing the ADP release rate constant. Thus, the reduction in the in vitro sliding velocity is likely due to a slowing of attachment rate. In muscle fiber studies we found that para-Nitroblebbistatin reduces steady-state force and calcium sensitivity but does not change maximum contractile velocity and the rate of force development. These results support a model in which the drug reduces the duty ratio without altering the kinetics of attached crossbridges. Thus, small molecule drugs that target the crossbridge attachment rate are an attractive strategy since they are capable of reducing the force generating capacity and calcium sensitivity without altering contractile velocity." @default.
- W2584701554 created "2017-02-10" @default.
- W2584701554 creator A5020062987 @default.
- W2584701554 creator A5046127236 @default.
- W2584701554 creator A5050201183 @default.
- W2584701554 creator A5072941379 @default.
- W2584701554 date "2017-02-01" @default.
- W2584701554 modified "2023-09-28" @default.
- W2584701554 title "Impact of Para-Nitroblebbistatin on Human Beta-Cardiac Myosin at the Molecular and Tissue Levels" @default.
- W2584701554 doi "https://doi.org/10.1016/j.bpj.2016.11.668" @default.
- W2584701554 hasPublicationYear "2017" @default.
- W2584701554 type Work @default.
- W2584701554 sameAs 2584701554 @default.
- W2584701554 citedByCount "0" @default.
- W2584701554 crossrefType "journal-article" @default.
- W2584701554 hasAuthorship W2584701554A5020062987 @default.
- W2584701554 hasAuthorship W2584701554A5046127236 @default.
- W2584701554 hasAuthorship W2584701554A5050201183 @default.
- W2584701554 hasAuthorship W2584701554A5072941379 @default.
- W2584701554 hasBestOaLocation W25847015541 @default.
- W2584701554 hasConcept C103486182 @default.
- W2584701554 hasConcept C12554922 @default.
- W2584701554 hasConcept C125705527 @default.
- W2584701554 hasConcept C126322002 @default.
- W2584701554 hasConcept C134018914 @default.
- W2584701554 hasConcept C160408235 @default.
- W2584701554 hasConcept C164705383 @default.
- W2584701554 hasConcept C174054327 @default.
- W2584701554 hasConcept C2778996579 @default.
- W2584701554 hasConcept C2780185194 @default.
- W2584701554 hasConcept C36036425 @default.
- W2584701554 hasConcept C39133596 @default.
- W2584701554 hasConcept C500558357 @default.
- W2584701554 hasConcept C6997183 @default.
- W2584701554 hasConcept C71924100 @default.
- W2584701554 hasConcept C7301908 @default.
- W2584701554 hasConcept C74581901 @default.
- W2584701554 hasConcept C8035138 @default.
- W2584701554 hasConcept C86803240 @default.
- W2584701554 hasConcept C95444343 @default.
- W2584701554 hasConceptScore W2584701554C103486182 @default.
- W2584701554 hasConceptScore W2584701554C12554922 @default.
- W2584701554 hasConceptScore W2584701554C125705527 @default.
- W2584701554 hasConceptScore W2584701554C126322002 @default.
- W2584701554 hasConceptScore W2584701554C134018914 @default.
- W2584701554 hasConceptScore W2584701554C160408235 @default.
- W2584701554 hasConceptScore W2584701554C164705383 @default.
- W2584701554 hasConceptScore W2584701554C174054327 @default.
- W2584701554 hasConceptScore W2584701554C2778996579 @default.
- W2584701554 hasConceptScore W2584701554C2780185194 @default.
- W2584701554 hasConceptScore W2584701554C36036425 @default.
- W2584701554 hasConceptScore W2584701554C39133596 @default.
- W2584701554 hasConceptScore W2584701554C500558357 @default.
- W2584701554 hasConceptScore W2584701554C6997183 @default.
- W2584701554 hasConceptScore W2584701554C71924100 @default.
- W2584701554 hasConceptScore W2584701554C7301908 @default.
- W2584701554 hasConceptScore W2584701554C74581901 @default.
- W2584701554 hasConceptScore W2584701554C8035138 @default.
- W2584701554 hasConceptScore W2584701554C86803240 @default.
- W2584701554 hasConceptScore W2584701554C95444343 @default.
- W2584701554 hasLocation W25847015541 @default.
- W2584701554 hasOpenAccess W2584701554 @default.
- W2584701554 hasPrimaryLocation W25847015541 @default.
- W2584701554 hasRelatedWork W2042542946 @default.
- W2584701554 hasRelatedWork W2075077936 @default.
- W2584701554 hasRelatedWork W2174308494 @default.
- W2584701554 hasRelatedWork W2213826337 @default.
- W2584701554 hasRelatedWork W2517821172 @default.
- W2584701554 hasRelatedWork W2563500873 @default.
- W2584701554 hasRelatedWork W2564270276 @default.
- W2584701554 hasRelatedWork W2571520799 @default.
- W2584701554 hasRelatedWork W2606113495 @default.
- W2584701554 hasRelatedWork W2735020447 @default.
- W2584701554 hasRelatedWork W2764138940 @default.
- W2584701554 hasRelatedWork W2796113416 @default.
- W2584701554 hasRelatedWork W2802235816 @default.
- W2584701554 hasRelatedWork W2806708786 @default.
- W2584701554 hasRelatedWork W2886773254 @default.
- W2584701554 hasRelatedWork W2911609398 @default.
- W2584701554 hasRelatedWork W3111162908 @default.
- W2584701554 hasRelatedWork W3113603657 @default.
- W2584701554 hasRelatedWork W3154691421 @default.
- W2584701554 hasRelatedWork W3165529164 @default.
- W2584701554 isParatext "false" @default.
- W2584701554 isRetracted "false" @default.
- W2584701554 magId "2584701554" @default.
- W2584701554 workType "article" @default.