Matches in SemOpenAlex for { <https://semopenalex.org/work/W2327173379> ?p ?o ?g. }
Showing items 1 to 73 of
73
with 100 items per page.
- W2327173379 endingPage "569a" @default.
- W2327173379 startingPage "569a" @default.
- W2327173379 abstract "Spontaneous firing of sinoatrial node cells (SANC) is controlled by sarcoplasmic reticulum (SR) generated local subsarcolemmal Ca2+ releases (LCRs), which appear during diastolic depolarization (DD) and activate an inward Na+-Ca2+exchange current to regulate DD and SANC beating rate. We have previously demonstrated that constitutive PLC activation is critical for regulation of Ca2+ cycling and spontaneous beating of rabbit SANC. PLC could be activated by multiple pathways, including the cAMP mediator, Epac, or activation of EGFR. Activation of Epac signaling by cpTOME, however, was without effect on the spontaneous SANC beating rate, ruling this pathway out. Whether EGFR is present in rabbit SANC or involved in the regulation of cardiac pacemaker function is unknown. Here we report that both EGFR and PLC (assessed by RNA-sequencing) are expressed in rabbit SANC. Specific EGFR inhibitor AG1478 decreased the DD rate and spontaneous SANC beating rate (perforated patch-clamp recordings). Furthermore, EGFR inhibition by AG1478, in a time-dependent manner, suppressed LCRs (confocal microscopy, Ca2+ indicator Fluo-3), i.e. decreased average LCR's size, number per each spontaneous cycle and prolonged the LCR period (the interval between AP-induced Ca2+ transient and subsequent LCR); and subsequently eliminated LCRs and abolished SANC firing. The time- dependent increase in the LCR period in response to AG1478 predicted the concomitant increase in the spontaneous cycle length, suggesting that Ca2+ cycling could be a major target of EGFR-PLC-dependent regulation of SANC firing. All effects of AG1478 were reversible upon washout. We conclude that basal EGFR-PLC-dependent regulation of SR Ca2+ cycling and LCR characteristics represent novel mechanism to control normal automaticity of cardiac pacemaker cells." @default.
- W2327173379 created "2016-06-24" @default.
- W2327173379 creator A5016204107 @default.
- W2327173379 creator A5045563275 @default.
- W2327173379 creator A5048711709 @default.
- W2327173379 date "2015-01-01" @default.
- W2327173379 modified "2023-09-29" @default.
- W2327173379 title "Basal Activity of Epidermal Growth Factor Receptor (EGFR) and Phospholipase C (PLC) are Required to Sustain Spontaneous Beating of Cardiac Pacemaker Cells" @default.
- W2327173379 doi "https://doi.org/10.1016/j.bpj.2014.11.3113" @default.
- W2327173379 hasPublicationYear "2015" @default.
- W2327173379 type Work @default.
- W2327173379 sameAs 2327173379 @default.
- W2327173379 citedByCount "0" @default.
- W2327173379 crossrefType "journal-article" @default.
- W2327173379 hasAuthorship W2327173379A5016204107 @default.
- W2327173379 hasAuthorship W2327173379A5045563275 @default.
- W2327173379 hasAuthorship W2327173379A5048711709 @default.
- W2327173379 hasBestOaLocation W23271733791 @default.
- W2327173379 hasConcept C12554922 @default.
- W2327173379 hasConcept C126322002 @default.
- W2327173379 hasConcept C134018914 @default.
- W2327173379 hasConcept C158617107 @default.
- W2327173379 hasConcept C170493617 @default.
- W2327173379 hasConcept C185592680 @default.
- W2327173379 hasConcept C197270303 @default.
- W2327173379 hasConcept C2777953023 @default.
- W2327173379 hasConcept C2778024521 @default.
- W2327173379 hasConcept C2778542873 @default.
- W2327173379 hasConcept C2779306644 @default.
- W2327173379 hasConcept C2779438470 @default.
- W2327173379 hasConcept C55493867 @default.
- W2327173379 hasConcept C71924100 @default.
- W2327173379 hasConcept C84393581 @default.
- W2327173379 hasConcept C86803240 @default.
- W2327173379 hasConcept C95444343 @default.
- W2327173379 hasConceptScore W2327173379C12554922 @default.
- W2327173379 hasConceptScore W2327173379C126322002 @default.
- W2327173379 hasConceptScore W2327173379C134018914 @default.
- W2327173379 hasConceptScore W2327173379C158617107 @default.
- W2327173379 hasConceptScore W2327173379C170493617 @default.
- W2327173379 hasConceptScore W2327173379C185592680 @default.
- W2327173379 hasConceptScore W2327173379C197270303 @default.
- W2327173379 hasConceptScore W2327173379C2777953023 @default.
- W2327173379 hasConceptScore W2327173379C2778024521 @default.
- W2327173379 hasConceptScore W2327173379C2778542873 @default.
- W2327173379 hasConceptScore W2327173379C2779306644 @default.
- W2327173379 hasConceptScore W2327173379C2779438470 @default.
- W2327173379 hasConceptScore W2327173379C55493867 @default.
- W2327173379 hasConceptScore W2327173379C71924100 @default.
- W2327173379 hasConceptScore W2327173379C84393581 @default.
- W2327173379 hasConceptScore W2327173379C86803240 @default.
- W2327173379 hasConceptScore W2327173379C95444343 @default.
- W2327173379 hasIssue "2" @default.
- W2327173379 hasLocation W23271733791 @default.
- W2327173379 hasOpenAccess W2327173379 @default.
- W2327173379 hasPrimaryLocation W23271733791 @default.
- W2327173379 hasRelatedWork W1969550954 @default.
- W2327173379 hasRelatedWork W2009854143 @default.
- W2327173379 hasRelatedWork W2016328345 @default.
- W2327173379 hasRelatedWork W2072392368 @default.
- W2327173379 hasRelatedWork W2077325982 @default.
- W2327173379 hasRelatedWork W2135024115 @default.
- W2327173379 hasRelatedWork W2150096959 @default.
- W2327173379 hasRelatedWork W2162653391 @default.
- W2327173379 hasRelatedWork W2411332413 @default.
- W2327173379 hasRelatedWork W2915913567 @default.
- W2327173379 hasVolume "108" @default.
- W2327173379 isParatext "false" @default.
- W2327173379 isRetracted "false" @default.
- W2327173379 magId "2327173379" @default.
- W2327173379 workType "article" @default.