A5051740332- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Signaling Pathways in Disease
- Cardiovascular Effects of Exercise
- Ion Channels and Receptors
- Cardiac Arrhythmias and Treatments
- Cardiomyopathy and Myosin Studies
- Chemotherapy-induced cardiotoxicity and mitigation
- Neuroscience and Neuropharmacology Research
- Cardiac pacing and defibrillation studies
- Cardiovascular Function and Risk Factors
- Phosphodiesterase function and regulation
- Hormonal Regulation and Hypertension
- Adipose Tissue and Metabolism
- Cardiac Ischemia and Reperfusion
- Respiratory viral infections research
- Prostate Cancer Treatment and Research
- Neonatal Respiratory Health Research
- Nitric Oxide and Endothelin Effects
- Cardiac Fibrosis and Remodeling
- Diabetes Management and Research
- Cancer Treatment and Pharmacology
- Calcium signaling and nucleotide metabolism
Université Paris-Saclay
2016-2025
Inserm
2016-2025
Laboratory Signaling and Cardiovascular Pathophysiology
2016-2025
University of California, Los Angeles
2008-2025
Hospital Universitario Virgen de la Arrixaca
2025
Los Angeles County Department of Health Services
2025
Hospital Universitario San Ignacio
2019-2024
Pontificia Universidad Javeriana
2008-2024
Zero Emissions Resource Organisation
2024
University Hospital Bonn
2024
Cardiac hypertrophy and heart failure caused by high blood pressure were studied in single myocytes taken from hypertensive rats (Dahl SS/Jr) SH-HF failure. Confocal microscopy patch-clamp methods used to examine excitation-contraction (EC) coupling, the relation between plasma membrane calcium current ( I Ca ) evoked release sarcoplasmic reticulum (SR), which was visualized as “calcium sparks.” The ability of trigger SR both hypertrophied failing hearts reduced. Because density...
Our recent data show that in cardiac myocytes polyunsaturated fatty acids (PUFAs) are antiarrhythmic. They reduce I Na , shorten the action potential, shift threshold for excitation to more positive potentials, and prolong relative refractory period. In this study we use patch-clamp techniques whole-cell mode confocal Ca 2+ imaging examine effects of PUFAs on voltage-gated L-type current ( Ca,L ), elementary sarcoplasmic reticulum -release events (Ca -sparks), [Ca ] i transients isolated rat...
Becker muscular dystrophy (BMD) is a variant of dystrophin deficiency resulting from DMD gene mutations. Phenotype variable with loss ambulation in late teenage or mid-life years. There currently no treatment for this condition. In BMD proof-of-principle clinical trial, potent myostatin antagonist, follistatin (FS), was used to inhibit the pathway. Extensive preclinical studies, using adeno-associated virus (AAV) deliver follistatin, demonstrated an increase strength. For we alternatively...
Cardiovascular disease is the leading cause of death in diabetic population. However, molecular mechanisms underlying cardiomyopathy remain unclear. We analyzed Ca2+-induced Ca2+ release and excitation-contraction coupling db/db obese type 2 mice their control littermates. Echocardiography showed a systolic dysfunction mice. Two-photon microscopy identified intracellular calcium concentration ([Ca2+]i) transient decrease cardiomyocytes within whole heart, which was also found isolated...
Abstract Ca 2+ sparks, the elementary events underlying excitation-contraction (E-C) coupling, occur when sarcoplasmic reticulum (SR) release channels open. They are activated locally by influx through sarcolemmal (SL) channels. By measuring probability of spark occurrence under conditions in which their is low, we address two important questions raised our recent work: (1) When a triggered, how many SL (at minimum) contribute to its activation? (2) What relation between subcellular local...
The cardiac ryanodine receptor/calcium release channel (RyR2) on the sarcoplasmic reticulum (SR) comprises a macromolecular complex that includes kinase and two phosphatases are bound to via targeting proteins. We previously found RyR2 is protein A (PKA)-hyperphosphorylated in end-stage human heart failure. Because failure progressive disease often evolves from hypertrophy, we analyzed several animal models of cardiomyopathy lead failure, including at different stages progression. now show...
cAMP is a powerful second messenger whose known general effector protein kinase A (PKA). The identification of binding protein, Epac, raises the question its role in Ca 2+ signalling cardiac myocytes. In this study, we analysed effects Epac activation on handling by using confocal microscopy isolated adult rat cardiomyocytes. [Ca ] i transients were evoked electrical stimulation and sparks measured quiescent was selectively activated analogue 8‐(4‐chlorophenylthio)‐2′‐ O...
Background — Heart failure (HF) frequently follows the occurrence of myocardial infarction (MI). Questions about how HF develops and what cellular defects contribute to this dysfunction led study. Methods Results MI was induced in rats by coronary artery ligation. Clinical examination post-MI (PMI) surviving animals indicated that they were overt all measures. Cellular cardiomyocytes patch-clamp confocal [Ca 2+ ] i imaging methods function significantly compromised. At single-cell level,...
Cardiac ryanodine receptor (RyR2) mutations are associated with autosomal dominant catecholaminergic polymorphic ventricular tachycardia, suggesting that alterations in Ca(2+) handling underlie this disease. Here we analyze the underlying release defect leads to arrhythmia cardiomyocytes isolated from heterozygous knock-in mice carrying RyR2(R4496C) mutation. RyR2(R4496C-/-) littermates (wild type) were used as controls. [Ca(2+)](i) transients obtained by field stimulation fluo-3-loaded and...
Infection by RNA viruses is detected the host through Toll-like receptors or RIG-I-like receptors. and signal adaptors MyD88 MAVS, respectively, to induce type I IFNs (IFN-I) other antiviral molecules, which are thought be essential for activating adaptive immune system. We investigated role of these in innate responses against respiratory syncytial virus (RSV), a common human pathogen. Deletion Mavs abolished induction IFN-I proinflammatory cytokines RSV. Genome-wide expression profiling...
Duchenne muscular dystrophy (DMD) typically occurs as a result of truncating mutations in the DMD gene that lack expression dystrophin protein muscle fibers. Various therapies under development are directed toward restoring at subsarcolemmal membrane, including transfer. In trial intramuscular adeno-associated virus (AAV)-mediated delivery therapeutic minidystrophin construct, we identified two six subjects presence population T cells had been primed to recognize epitopes before transgene...
Monoallelic mutations in the gene encoding bone morphogenetic protein receptor 2 ( Bmpr2) are main genetic risk factor for heritable pulmonary arterial hypertension (PAH) with incomplete penetrance. Several Bmpr2 transgenic mice have been reported to develop mild spontaneous PAH. In this study, we examined whether rats mutation were susceptible developing more severe PAH.The zinc finger nuclease method was used establish rat lines gene. These then characterized at hemodynamic, histological,...
Although cardiac cytosolic cyclic 3',5'-adenosine monophosphate (cAMP) regulates multiple processes, such as beating, contractility, metabolism and apoptosis, little is known yet on the role of this second messenger within mitochondria. Using cellular subcellular approaches, we demonstrate here local expression several actors cAMP signaling mitochondria, namely a truncated form soluble AC (sACt) exchange protein directly activated by 1 (Epac1), show protective for sACt against cell death,...
Sino-atrial node (SAN) automaticity is an essential mechanism of heart rate generation that still not completely understood. Recent studies highlighted the importance intracellular Ca2+ ([Ca2+]i) dynamics during SAN pacemaker activity. Nevertheless, functional role voltage-dependent L-type channels in controlling [Ca2+]i release largely unexplored. Since Cav1.3 predominant channel isoform cells, we studied isolated cells and ex vivo preparations explanted from wild-type (WT) knockout (KO)...
Respiratory syncytial virus (RSV) infection is associated with acute morbidity (e.g., pneumonia and airway obstruction [AO]) long-term complications hyperresponsiveness [AHR]). We present a comprehensive evaluation of the chronic phases RSV respiratory tract infection, using mouse model.BALB/c mice were inoculated monitored for 154 days. loads cytokines measured in bronchoalveolar lavage (BAL) samples. Pneumonia severity was assessed standard histopathologic score, pulmonary function...
The tetrodotoxin-sensitive sodium ion (Na + ) channel is opened by cellular depolarization and favors the passage of Na over other ions. Activation β-adrenergic receptor or protein kinase A in rat heart cells transformed this into one that promiscuous with respect to selectivity, permitting calcium ions (Ca 2+ permeate as readily . Similarly, nanomolar concentrations cardiotonic steroids such ouabain digoxin switched selectivity state permeability called slip-mode conductance. Slip-mode...
1. The nature, magnitude and kinetics of the 4‐aminopyridine‐sensitive early outward current (Ito) were analysed in isolated ventricular myocytes from septum, apex left free wall rat ventricles using whole‐cell voltage clamp method. modulatory effect pressure overload‐induced cardiac hypertrophy on regional variations Ito was assessed each topographical class cells. 2. Voltage experiments performed at room temperature (20‐25 degrees C) absence Na+ both sides membrane presence 3 mM CoCl2....
Cardiac hypertrophy underlies arrhythmias and sudden death, for which mineralocorticoid receptor (MR) activity has recently been implicated. We sought to establish the sequence of ionic events that link initiating insult MR development.Using whole-cell, patch-clamp quantitative reverse transcription-polymerase chain reaction techniques on right ventricular myocytes a myocardial infarction (MI) rat model, we examined cellular response over time. One week after MI, no sign was found, but...
The mineralocorticoid pathway is involved in cardiac arrhythmias associated with heart failure through mechanisms that are incompletely understood. Defective regulation of the ryanodine receptor (RyR) an important cause initiation arrhythmias. Here, we examined whether aldosterone might modulate RyR function.Using whole-cell patch clamp method, observed increase occurrence delayed afterdepolarizations during action potential recordings isolated adult rat ventricular myocytes exposed for 48...
Phosphoinositide 3-kinase γ (PI3Kγ) signaling engaged by β-adrenergic receptors is pivotal in the regulation of myocardial contractility and remodeling. However, role PI3Kγ catecholamine-induced arrhythmia currently unknown.Mice lacking (PI3Kγ(-/-)) showed runs premature ventricular contractions on adrenergic stimulation that could be rescued a selective β(2)-adrenergic receptor blocker developed sustained tachycardia after transverse aortic constriction. Consistently, fluorescence resonance...
Background— Catecholaminergic polymorphic ventricular tachycardia is characterized by stress-triggered syncope and sudden death. Patients with catecholaminergic manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored. Methods Results— We investigated SAN [Ca 2+ ] i handling in mice carrying tachycardia–linked mutation ryanodine receptor (RyR2 R4496C ) their wild-type (WT) littermates. In vivo telemetric recordings showed impaired automaticity RyR2 after...