Matches in SemOpenAlex for { <https://semopenalex.org/work/W2510122736> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W2510122736 endingPage "274a" @default.
- W2510122736 startingPage "273a" @default.
- W2510122736 abstract "The spontaneous SANC beating rate is controlled by cAMP-mediated, PKA-dependent (cAMP/PKA) LCRs from ryanodine receptors (RyR). LCRs activate an inward Na+/Ca2+ exchange current increasing diastolic depolarization (DD) rate and spontaneous SANC firing. High basal level of cAMP in SANC is regulated by high phosphodiesterase (PDE) activity. In rat ventricular myocytes (VM) dual inhibition of both PDE3 and PDE4 synergistically increased the contraction amplitude. We studied whether PDE3 alone or concurrent (PDE3+PDE4) activation regulated spontaneous firing of rabbit SANC. Specific PDE3 inhibitor (cilostomide) or PDE4 inhibitor (rolipram) alone increased spontaneous firing (perforated patch-clamp) by only∼20% and ∼5%, respectively. But concurrent (PDE3+PDE4) inhibition increased spontaneous firing by∼48% accompanied by increases in LCR number, size and decrease in the LCR period that predicted concomitant reduction in SANC cycle length. In permeabilized SANC inhibition of PDE3 or PDE4 alone produced minor changes in LCR characteristics, while concurrent (PDE3+PDE4) inhibition markedly increased LCR size and number. Inhibition of PDE3 or PDE4 alone increased phospholamban (PLB) phosphorylation at Ser16site (marker of cAMP/PKA-dependent phosphorylation) by∼20%; inhibition of (PDE3+PDE4), however, increased PLB phosphorylation by∼110%. L-type Ca2+ current (ICa,L) provides Ca2+available for pumping into sarcoplasmic reticulum. PDE3 or PDE4 inhibition alone increased ICa,L amplitude by∼60% and∼5%, respectively, while concurrent (PDE3+PDE4) inhibition increased ICa,L by∼100%. When RyR were disabled by ryanodine (PDE3+PDE4) inhibition failed to increase SANC firing rate. Western blots revealed diverse expression of PDE subtypes in SA node and ventricle: more PDE4D was expressed in former, but more PDE3A in the latter; PDE4B was similarly expressed in both tissues. Thus, concurrent (PDE3+PDE4) activation regulates spontaneous SANC firing in a synergistic manner, by suppressing basal cAMP/PKA-dependent phosphorylation, reducing RyR Ca2+release and prolonging the LCR period and spontaneous cycle length." @default.
- W2510122736 created "2016-09-16" @default.
- W2510122736 creator A5010362119 @default.
- W2510122736 creator A5016204107 @default.
- W2510122736 creator A5044098068 @default.
- W2510122736 creator A5044367029 @default.
- W2510122736 creator A5045563275 @default.
- W2510122736 creator A5048711709 @default.
- W2510122736 creator A5061406584 @default.
- W2510122736 date "2016-02-01" @default.
- W2510122736 modified "2023-09-27" @default.
- W2510122736 title "Concurrent PDE3 and PDE4 Activation Suppresses Local Ca2+ Releases (LCR) to Regulate Normal Spontaneous Firing of Sinoatrial Node Cells (SANC)" @default.
- W2510122736 doi "https://doi.org/10.1016/j.bpj.2015.11.1485" @default.
- W2510122736 hasPublicationYear "2016" @default.
- W2510122736 type Work @default.
- W2510122736 sameAs 2510122736 @default.
- W2510122736 citedByCount "0" @default.
- W2510122736 crossrefType "journal-article" @default.
- W2510122736 hasAuthorship W2510122736A5010362119 @default.
- W2510122736 hasAuthorship W2510122736A5016204107 @default.
- W2510122736 hasAuthorship W2510122736A5044098068 @default.
- W2510122736 hasAuthorship W2510122736A5044367029 @default.
- W2510122736 hasAuthorship W2510122736A5045563275 @default.
- W2510122736 hasAuthorship W2510122736A5048711709 @default.
- W2510122736 hasAuthorship W2510122736A5061406584 @default.
- W2510122736 hasBestOaLocation W25101227361 @default.
- W2510122736 hasConcept C113217602 @default.
- W2510122736 hasConcept C11960822 @default.
- W2510122736 hasConcept C126322002 @default.
- W2510122736 hasConcept C134018914 @default.
- W2510122736 hasConcept C170493617 @default.
- W2510122736 hasConcept C17137333 @default.
- W2510122736 hasConcept C181199279 @default.
- W2510122736 hasConcept C185592680 @default.
- W2510122736 hasConcept C24998067 @default.
- W2510122736 hasConcept C2776958096 @default.
- W2510122736 hasConcept C2779276759 @default.
- W2510122736 hasConcept C2781298581 @default.
- W2510122736 hasConcept C55493867 @default.
- W2510122736 hasConcept C58141971 @default.
- W2510122736 hasConcept C62826618 @default.
- W2510122736 hasConcept C71924100 @default.
- W2510122736 hasConcept C86803240 @default.
- W2510122736 hasConceptScore W2510122736C113217602 @default.
- W2510122736 hasConceptScore W2510122736C11960822 @default.
- W2510122736 hasConceptScore W2510122736C126322002 @default.
- W2510122736 hasConceptScore W2510122736C134018914 @default.
- W2510122736 hasConceptScore W2510122736C170493617 @default.
- W2510122736 hasConceptScore W2510122736C17137333 @default.
- W2510122736 hasConceptScore W2510122736C181199279 @default.
- W2510122736 hasConceptScore W2510122736C185592680 @default.
- W2510122736 hasConceptScore W2510122736C24998067 @default.
- W2510122736 hasConceptScore W2510122736C2776958096 @default.
- W2510122736 hasConceptScore W2510122736C2779276759 @default.
- W2510122736 hasConceptScore W2510122736C2781298581 @default.
- W2510122736 hasConceptScore W2510122736C55493867 @default.
- W2510122736 hasConceptScore W2510122736C58141971 @default.
- W2510122736 hasConceptScore W2510122736C62826618 @default.
- W2510122736 hasConceptScore W2510122736C71924100 @default.
- W2510122736 hasConceptScore W2510122736C86803240 @default.
- W2510122736 hasIssue "3" @default.
- W2510122736 hasLocation W25101227361 @default.
- W2510122736 hasOpenAccess W2510122736 @default.
- W2510122736 hasPrimaryLocation W25101227361 @default.
- W2510122736 hasRelatedWork W1967982155 @default.
- W2510122736 hasRelatedWork W1982310992 @default.
- W2510122736 hasRelatedWork W1988408001 @default.
- W2510122736 hasRelatedWork W2096227816 @default.
- W2510122736 hasRelatedWork W2116714338 @default.
- W2510122736 hasRelatedWork W2145573089 @default.
- W2510122736 hasRelatedWork W2324044573 @default.
- W2510122736 hasRelatedWork W2510122736 @default.
- W2510122736 hasRelatedWork W2805868398 @default.
- W2510122736 hasRelatedWork W2891576964 @default.
- W2510122736 hasVolume "110" @default.
- W2510122736 isParatext "false" @default.
- W2510122736 isRetracted "false" @default.
- W2510122736 magId "2510122736" @default.
- W2510122736 workType "article" @default.