ArticleThe Journal of physiology2004
Pacing-induced calcineurin activation controls cardiac Ca2+ signalling and gene expression.
Article in The Journal of physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
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- Emergent activity, heterogeneity, and robustness in a calcium feedback model of the sinoatrial node.Biophysical journal · 2023Article
- Inositol Trisphosphate Receptors and Nuclear Calcium in Atrial Fibrillation.Circulation research · 2021Article
- Calcium Signaling in Cardiomyocyte Function.Cold Spring Harbor perspectives in biology · 2020Review
- Mechanical regulation of gene expression in cardiac myocytes and fibroblasts.Nature reviews. Cardiology · 2019Review
- Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.Pflugers Archiv : European journal of physiology · 2016Article
- Calcium signalling in developing cardiomyocytes: implications for model systems and disease.The Journal of physiology · 2015Review
- Rate-dependent Ca2+ signalling underlying the force-frequency response in rat ventricular myocytes: a coupled electromechanical modeling study.Theoretical biology & medical modelling · 2013Article
- Visualizing CaMKII and CaM activity: a paradigm of compartmentalized signaling.Journal of molecular medicine (Berlin, Germany) · 2013Review
- MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation.The Journal of clinical investigation · 2013Article
- Understanding the pathogenesis of Kawasaki disease by network and pathway analysis.Computational and mathematical methods in medicine · 2013Review
- Ca(2+) influx through L-type Ca(2+) channels and transient receptor potential channels activates pathological hypertrophy signaling.Journal of molecular and cellular cardiology · 2012Article
- Calmodulin binding proteins provide domains of local Ca2+ signaling in cardiac myocytes.Journal of molecular and cellular cardiology · 2012Review
- The role of in vivo Ca²⁺ signals acting on Ca²⁺-calmodulin-dependent proteins for skeletal muscle plasticity.The Journal of physiology · 2011Review
- Accelerated development of pressure overload-induced cardiac hypertrophy and dysfunction in an RyR2-R176Q knockin mouse model.Hypertension (Dallas, Tex. : 1979) · 2010Article
- Regulation of nuclear factor of activated T cells (NFAT) in vascular endothelial cells.Journal of molecular and cellular cardiology · 2009Article
- Regulation of excitation-contraction coupling in mouse cardiac myocytes: integrative analysis with mathematical modelling.BMC physiology · 2009Article
- Sensitivity of NFAT cycling to cytosolic calcium concentration: implications for hypertrophic signals in cardiac myocytes.Biophysical journal · 2009Article
- Model of excitation-contraction coupling of rat neonatal ventricular myocytes.Biophysical journal · 2009Article
- Calmodulin mediates differential sensitivity of CaMKII and calcineurin to local Ca2+ in cardiac myocytes.Biophysical journal · 2008Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcineurin, a Ca(2+)-calmodulin-dependent protein phosphatase (PP2B) is one of the links between Ca(2+) signals and regulation of gene transcription in cardiac muscle. We studied the Ca(2+) signal specificity of calcineurin activation experimentally and with modelling. In the rat atrial preparation, an increase in pacing frequency increased nuclear activity of the calcineurin-sensitive transcription factor, nuclear factor of activated T-cells (NFAT), 2-fold in a cyclosporin A (CsA)-sensitive manner. In line with this, modelling results predicted that the frequency of cardiac Ca(2+) transients encodes the stimulus for calcineurin activation. We further observed experimentally that calcineurin inhibition by CsA modulated Ca(2+) release in a Ca(2+)-dependent manner. CsA had no effect on [Ca(2+)](i) at a pacing frequency of 1 Hz but it significantly suppressed the amplitude of Ca(2+) transients, systolic [Ca(2+)](i) and time averaged [Ca(2+)](i) at 6 Hz. Calcineurin had a differential role in the expression of immediate-early genes B-type natriuretic peptide (BNP) and c-fos. CsA inhibited the pacing-induced BNP gene expression, whereas pacing alone had no effect on the expression of c-fos. However, in the presence of CsA, c-fos mRNA levels were significantly augmented by increased pacing frequency. These results show that frequency-dependent calcineurin activation has a specific role in [Ca(2+)](i) regulation and gene expression, constantly recruited by varying cardiac Ca(2+) signals.
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