ArticleJournal of molecular and cellular cardiology2007
Temporal dissociation of frequency-dependent acceleration of relaxation and protein phosphorylation by CaMKII.
Article in Journal of molecular and cellular cardiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 81 citations in OpenAlex.
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- Dantrolene inhibition of ryanodine channels (RyR2) in artificial lipid bilayers depends on FKBP12.6.The Journal of general physiology · 2023Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling.Quarterly reviews of biophysics · 2023Review
- Nitrosylation of cardiac CaMKII at Cys290 mediates mechanical afterload-induced increases in CaThe Journal of physiology · 2022Article
- Loss of CASK Accelerates Heart Failure Development.Circulation research · 2021Article
- Multisite phosphorylation of the cardiac ryanodine receptor: a random or coordinated event?Pflugers Archiv : European journal of physiology · 2020Review
- Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats.Cell calcium · 2020Article
- CaMKIIδC Drives Early Adaptive CaCirculation research · 2020Article
- A Mathematical Model of the Mouse Atrial Myocyte With Inter-Atrial Electrophysiological Heterogeneity.Frontiers in physiology · 2020Article
- Conduction in the right and left ventricle is differentially regulated by protein kinases and phosphatases: implications for arrhythmogenesis.American journal of physiology. Heart and circulatory physiology · 2019Article
- Cardiac CaMKII activation promotes rapid translocation to its extra-dyadic targets.Journal of molecular and cellular cardiology · 2018Article
- Cardiac Protection of Valsartan on Juvenile Rats with Heart Failure by Inhibiting Activity of CaMKII via Attenuating Phosphorylation.BioMed research international · 2017Article
- Regulation of sarcoplasmic reticulum CaJournal of molecular and cellular cardiology · 2016Review
- Complement Destabilizes Cardiomyocyte Function In Vivo after Polymicrobial Sepsis and In Vitro.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- The calcium-frequency response in the rat ventricular myocyte: an experimental and modelling study.The Journal of physiology · 2016Article
- Atrial remodelling in atrial fibrillation: CaMKII as a nodal proarrhythmic signal.Cardiovascular research · 2016Review
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2 authors at 1 institution in 1 country.
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Abstract
Frequency-dependent acceleration of relaxation (FDAR) is an important intrinsic mechanism that allows for diastolic filling of the ventricle at higher heart rates, yet its molecular mechanism is still not understood. Previous studies showed that FDAR is dependent on functional sarcoplasmic reticulum (SR) and can be abolished by phosphatase or by Ca/CaM kinase (CaMKII) inhibition. Additionally, CaMKII activity/autophosphorylation has been shown to be frequency-dependent. Thus, we tested the hypothesis that CaMKII phosphorylation of SR Ca(2+)-handling proteins (Phospholamban (PLB), Ca(2+) release channel (RyR)) mediates FDAR. Here we show that FDAR occurs abruptly in fluo-4 loaded isolated rat ventricular myocytes when frequency is raised from 0.1 to 2 Hz. The effect is essentially complete within four beats (2 s) with the tau of [Ca(2+)](i) decline decreasing by 42+/-3%. While there is a detectable increase in PLB Thr-17 and RyR Ser-2814 phosphorylation, the increase is quantitatively small (PLB<5%, RyR approximately 8%) and the time-course is clearly delayed with regard to FDAR. The low substrate phosphorylation indicates that pacing of myocytes only mildly activates CaMKII and consistent with this CaMKIIdelta autophosphorylation did not increase with pacing alone. However, in the presence of phosphatase 1 inhibition pacing triggered a net-increase in autophosphorylated CaMKII and also greatly enhanced PLB and RyR phosphorylation. We conclude that FDAR does not rely on phosphorylation of PLB or RyR. Even though CaMKII does become activated when myocytes are paced, phosphatases immediately antagonize CaMKII action, limit substrate phosphorylation and also prevent sustained CaMKII autophosphorylation (thereby suppressing global CaMKII effects).
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