Cyclic AMP signaling in cardiac myocytes

International audienceThe cyclic nucleotide 3′,5′-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger of paramount importance in the regulation of the cardiac pump. It is now well established that cAMP is confined in specific subcellular compartments where it modulates various targets associated in signalosomes to control, for example, excitation–contraction coupling or gene transcription. In this review, we summarize notable breakthroughs on how cAMP is synthesized, degraded and compartmentalized. We describe its effectors, including newly described targets with emerging roles in heart. We also briefly discuss innovative methods recently developed to bring new insights on the role of these cAMP microdomains to control cardiac function

John Erskine (1879-1951) : constitution d’une bibliothèque américaine à l’Université de Bourgogne (1954)

Quelques marques de provenances américaines dans une bibliothèque universitaire française À la bibliothèque de l’Université de Dijon, les collections américaines sont, soit intégrées dans le fonds général, soit constituées en fonds particulier. Ce dernier a pour caractéristiques, d’une part de refléter l’histoire d’une personne ou d’une institution, d’autre part d’être traité (signalement, conservation) comme un ensemble clos. Concernant le premier cas de figure, on peut citer un lot d’ouvrag..

Optimisation des empilements dans les structures composites stratifiées avec arrêts de plis

http://www.emse.fr/~leriche/JNC18_IRISARRI_Article_8.pdfCet article introduit le concept de table de drapage pour la conception optimale de structures composites stratifiées avec arrêts de plis. La table de drapage décrit la série des arrêts de plis assurant la transition entre un empilement maître épais et un empilement plus fin. Une structure stratifiée d'épaisseur variable est représentée par une table de drapage combinée à une distribution d'épaisseur sur les régions de la structure. Un algorithme évolutionnaire est spécialisé pour l'optimisation des tables de drapage. L'optimisation de la série des arrêts de plis à l'aide de l'algorithme proposé permet de satisfaire des règles de conception qui n'avaient pu être introduites dans les études publiées à ce jour. Un large ensemble de règles de conception, représentatif des exigences industrielles actuelles, est introduit. La méthode est appliquée à un cas -test de la littérature, composé de 18 panneaux, avec des résultats convaincants. En particulier, ces résultats montrent que les règles de conception peuvent être appliquées sans pénaliser significativement le comportement en raideur et la masse de la structure

Imipramine as an alternative to formamide to detubulate rat ventricular cardiomyocytes

International audienceT-tubules are membrane invaginations essential for the excitation-contraction coupling (ECC). Imipramine like other cationic amphiphilic drugs, interfere with the PI(4,5)P2 interactions with proteins maintaining the tubular system connected to cell surface. Our main purpose was to validate imipramine as a new detubulating agent in cardiomyocytes. Staining adult rat ventricular myocytes (ARVMs) with di-4-ANEPPS, we showed that unlike formamide, imipramine induces a complete detubulation with no impact on cell viability. Using the patch-clamp technique, we observed a ~40% decrease in cell capacitance after imipramine pretreatment and a reduction of ICa,L Disclaimer: This is a confidential document

Knowledge gaps in economic costs of invasive alien fish worldwide

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Synergic PDE3 and PDE4 control intracellular cAMP and cardiac excitation-contraction coupling in a porcine model

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Interventricular Differences in β‐Adrenergic Responses in the Canine Heart: Role of Phosphodiesterases

Background RV and LV have different embryologic, structural, metabolic, and electrophysiologic characteristics, but whether interventricular differences exist in β‐adrenergic (β‐AR) responsiveness is unknown. In this study, we examine whether β‐AR response and signaling differ in right (RV) versus left (LV) ventricles. Methods and Results Sarcomere shortening, Ca2+ transients, ICa,L and IKs currents were recorded in isolated dog LV and RV midmyocytes. Intracellular [cAMP] and PKA activity were measured by live cell imaging using FRET‐based sensors. Isoproterenol increased sarcomere shortening ≈10‐fold and Ca2+‐transient amplitude ≈2‐fold in LV midmyocytes (LVMs) versus ≈25‐fold and ≈3‐fold in RVMs. FRET imaging using targeted Epac2camps sensors revealed no change in subsarcolemmal [cAMP], but a 2‐fold higher β‐AR stimulation of cytoplasmic [cAMP] in RVMs versus LVMs. Accordingly, β‐AR regulation of ICa,L and IKs were similar between LVMs and RVMs, whereas cytoplasmic PKA activity was increased in RVMs. Both PDE3 and PDE4 contributed to the β‐AR regulation of cytoplasmic [cAMP], and the difference between LVMs and RVMs was abolished by PDE3 inhibition and attenuated by PDE4 inhibition. Finally LV and RV intracavitary pressures were recorded in anesthetized beagle dogs. A bolus injection of isoproterenol increased RV dP/dtmax≈5‐fold versus 3‐fold in LV. Conclusion Canine RV and LV differ in their β‐AR response due to intrinsic differences in myocyte β‐AR downstream signaling. Enhanced β‐AR responsiveness of the RV results from higher cAMP elevation in the cytoplasm, due to a decreased degradation by PDE3 and PDE4 in the RV compared to the LV

Phosphodiesterase 2 Protects against Catecholamine-induced Arrhythmias and Preserves Contractile Function after Myocardial Infarction

International audienceRationale: Phosphodiesterase 2 is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyzes cAMP. Myocardial phosphodiesterase 2 is upregulated in human heart failure, but its role in the heart is unknown.Objective: To explore the role of phosphodiesterase 2 in cardiac function, propensity to arrhythmia, and myocardial infarction.Methods and Results: Pharmacological inhibition of phosphodiesterase 2 (BAY 60–7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor activation in healthy mice. Under pathological conditions induced by chronic catecholamine infusions, BAY reversed both the attenuated β-adrenoceptor–mediated inotropy and chronotropy. Conversely, ECG telemetry in heart-specific phosphodiesterase 2-transgenic (TG) mice showed a marked reduction in resting and in maximal heart rate, whereas cardiac output was completely preserved because of greater cardiac contraction. This well-tolerated phenotype persisted in elderly TG with no indications of cardiac pathology or premature death. During arrhythmia provocation induced by catecholamine injections, TG animals were resistant to triggered ventricular arrhythmias. Accordingly, Ca2+-spark analysis in isolated TG cardiomyocytes revealed remarkably reduced Ca2+ leakage and lower basal phosphorylation levels of Ca2+-cycling proteins including ryanodine receptor type 2. Moreover, TG demonstrated improved cardiac function after myocardial infarction.Conclusions: Endogenous phosphodiesterase 2 contributes to heart rate regulation. Greater phosphodiesterase 2 abundance protects against arrhythmias and improves contraction force after severe ischemic insult. Activating myocardial phosphodiesterase 2 may, thus, represent a novel intracellular antiadrenergic therapeutic strategy protecting the heart from arrhythmia and contractile dysfunction

Global economic costs of aquatic invasive alien species

Much research effort has been invested in understanding ecological impacts of invasive alien species (IAS) across ecosystems and taxonomic groups, but empirical studies about economic effects lack synthesis. Using a comprehensive global database, we determine patterns and trends in economic costs of aquatic IAS by examining: (i) the distribution of these costs across taxa, geographic regions and cost types; (ii) the temporal dynamics of global costs; and (iii) knowledge gaps, especially compared to terrestrial IAS. Based on the costs recorded from the existing literature, the global cost of aquatic IAS conservatively summed to US$345 billion, with the majority attributed to invertebrates (62$23 billion in 2020. Costs are likely considerably underrepresented compared to terrestrial IAS; only 5% of reported costs were from aquatic species, despite 26% of known invaders being aquatic. Additionally, only 1% of aquatic invasion costs were from marine species. Costs of aquatic IAS are thus substantial, but likely underreported. Costs have increased over time and are expected to continue rising with future invasions. We urge increased and improved cost reporting by managers, practitioners and researchers to reduce knowledge gaps. Few costs are proactive investments; increased management spending is urgently needed to prevent and limit current and future aquatic IAS damages. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe