A5078340269- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Nicotinic Acetylcholine Receptors Study
- Cardiomyopathy and Myosin Studies
- Neuroscience and Neuropharmacology Research
- Glycosylation and Glycoproteins Research
- Neuroscience and Neural Engineering
- Cardiovascular Effects of Exercise
- Galectins and Cancer Biology
- Receptor Mechanisms and Signaling
- Sepsis Diagnosis and Treatment
- SARS-CoV-2 and COVID-19 Research
- Venomous Animal Envenomation and Studies
- Pharmacological Receptor Mechanisms and Effects
- Insect and Pesticide Research
- Photoreceptor and optogenetics research
- Photochromic and Fluorescence Chemistry
- Metabolomics and Mass Spectrometry Studies
- Immune Response and Inflammation
- S100 Proteins and Annexins
- COVID-19 Clinical Research Studies
- Marine Toxins and Detection Methods
- Monoclonal and Polyclonal Antibodies Research
- Bacillus and Francisella bacterial research
- Viral Infections and Outbreaks Research
Inserm
2015-2025
Institut du Thorax
2015-2025
Nantes Université
2010-2025
Centre National de la Recherche Scientifique
2012-2025
Laboratoire d'Excellence Canaux Ioniques d'Intérêt Thérapeutique
2022-2024
Centre Hospitalier Universitaire de Nantes
2023
Institut de Pharmacologie Moléculaire et Cellulaire
2022
New York University
2017-2018
Plakophilin-2 (PKP2) is a component of the desmosome and known for its role in cell-cell adhesion. Mutations human PKP2 associate with life-threatening arrhythmogenic cardiomyopathy, often right ventricular predominance. Here, we use range state-of-the-art methods cardiomyocyte-specific, tamoxifen-activated, knockout mouse to demonstrate that addition cell adhesion, necessary maintain transcription genes control intracellular calcium cycling. Lack reduces expression Ryr2 (coding Ryanodine...
Plakophilin-2 (PKP2) is classically defined as a desmosomal protein. Mutations in PKP2 associate with most cases of gene-positive arrhythmogenic right ventricular cardiomyopathy. A better understanding cardiac biology can help elucidate the mechanisms underlying arrhythmic and cardiomyopathic events consequent to deficiency. Here, we sought capture early molecular/cellular that act nascent arrhythmic/cardiomyopathic substrates.We used multiple imaging, biochemical high-resolution mass...
Abstract Photoactivatable drugs targeting ligand-gated ion channels open up new opportunities for light-guided therapeutic interventions. Photoactivable toxins have the potential to control excitable cell activities with low invasiveness and high spatiotemporal precision. As proof-of-concept, we develop HwTxIV-Nvoc, a UV light-cleavable photoactivatable peptide that targets voltage-gated sodium (Na V ) validate its activity in vitro HEK293 cells, ex vivo brain slices on mice neuromuscular...
In neocortical layer-5 pyramidal neurons, the action potential (AP) is generated in axon initial segment (AIS) when membrane (Vm ) reaches threshold for activation of voltage-gated Na+ channels (VGNCs) Nav 1.2 and 1.6. Yet, whereas these VGNCs are known to differ spatial distribution along AIS biophysical properties, our understanding functional differences between two remains elusive. Here, using ultrafast , Vm Ca2+ imaging combination with partial block by peptide G1 G4 -huwentoxin-IV, we...
Natural peptides from animal venoms effectively modulate ion channel activity. While photoswitches regulate small compound pharmacology, their application to natural rich in disulfide bridges and active on channels is novel due larger pharmacophores. A pilot study integrating azobenzene into charybdotoxin (ChTx), known for blocking potassium initiated. Two click-chemistry-compatible are synthesized differing length amide orientation (Az1 & Az2). Az1 grafted onto ChTx at various amino acid...
Abstract Natural peptides from animal venoms effectively modulate ion channel activity. While photoswitches regulate small compound pharmacology, their application to natural rich in disulfide bridges and active on channels is novel due larger pharmacophores. A pilot study integrating azobenzene into charybdotoxin (ChTx), known for blocking potassium initiated. Two click‐chemistry‐compatible are synthesized differing length amide orientation (Az 1 & Az 2 ). grafted onto ChTx at various...
This study highlights the complementarity of automated patch-clamp (APC) and manual (MPC) approaches to describe electrophysiological properties eighteen Cav3.1 calcium channel variants associated with various neurological conditions. Current density was measured efficiently for all in APC experiments, four (p.V184G, p.N1200S, p.S1263A p.D2242N) showing high current densities, compared wild-type channel, while six (p.M197R, p.V392M, p.F956del, p.I962N, p.I1412T, p.G1534D) displayed low were...
Mutations of SCN5A gene, which encodes the α-subunit voltage-gated Na(+) channel Na(V)1.5, underlie hereditary cardiac arrhythmic syndromes such as type 3 long QT syndrome, conduction diseases, Brugada sick sinus a trial standstill, and numerous overlap syndromes. Patch-clamp studies in heterologous expression systems have provided important information to understand genotype-phenotype relationships these diseases. However, they could not clarify how mutations can be responsible for large...
Loss-of-function mutations in SCN5A, the gene encoding NaV1.5 channel, have been associated with inherited progressive cardiac conduction disease (PCCD). We proposed that Scn5a heterozygous knock-out (Scn5a+/-) mice, which are characterized by ventricular fibrotic remodelling ageing, represent a model for PCCD. Our objectives were to identify molecular pathway involved fibrosis development and prevent its activation.Our study shows myocardial interstitial occurred Scn5a+/- mice only after 45...
The patch-clamp technique and more recently the high throughput have contributed to major advances in characterization of ion channels. However, whole-cell voltage-clamp presents certain limits that need be considered for robust data generation. One caveat is increasing current amplitude profoundly impacts accuracy biophysical analyses macroscopic currents under study. Using mathematical kinetic models a cardiac voltage-gated sodium channel potassium channel, we demonstrated how large series...
Sepsis in the young population, which is particularly at risk, rarely studied. O-GlcNAcylation a post-translational modification involved cell survival, stress response and metabolic regulation. O-GlcNAc stimulation beneficial adult septic rats. This physiologically higher rat, potentially limiting therapeutic potential of The aim to evaluate whether can improve sepsis outcome Endotoxemic challenge was induced 28-day-old rats by lipopolysaccharide injection (E. Coli O111:B4, 20 mg·kg−1)...
◼ photochemotherapy potassium channels zebrafish
Previous studies in murine hearts and cell systems have shown that modifications the expression or sequence integrity of desmosomal molecule plakophilin-2 (PKP2) can alter downstream transcripts necessary for electrical mechanical function heart. These findings provided support to mechanistic hypotheses seek explain arrhythmogenic right ventricular cardiomyopathy (ARVC) humans. However, relation between PKP2 transcriptome human heart remains poorly explored. Furthermore, while a number...
Phlotoxin-1 (PhlTx1) is a peptide previously identified in tarantula venom (Phlogius species) that belongs to the inhibitory cysteine-knot (ICK) toxin family. Like many ICK-based spider toxins, synthesis of PhlTx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide bridge formation. Herein, we describe procedure chemical directed sequential formation allows straightforward production this challenging peptide. We also performed...
Metabolic sources switch from carbohydrates in utero, to fatty acids after birth and then a mix once adults. O-GlcNAcylation (O-GlcNAc) is post-translational modification considered as nutrient sensor. The purpose of this work was assess changes protein O-GlcNAc levels, regulatory enzymes metabolites during the first periods life decipher impact on cardiac proteins.Heart, brain liver were harvested rats before (D-1 D0), suckling animals (D12), weaning with standard (D28) or low-carbohydrate...
Abstract In intensive care units, COVID‐19 viral pneumonia patients (VPP) present symptoms similar to those of other with Nonviral infection (NV‐ICU). To better manage VPP, it is therefore interesting understand the molecular pathophysiology and search for biomarkers that may clarify diagnosis. The secretome being a set proteins secreted by cells in response stimuli represents an opportunity discover new biomarkers. objective this study identify secretomic signatures VPP NV‐ICU. Plasma...
Coronavirus disease of 2019 (COVID-19) has rapidly become a worldwide pandemic. Many clinical trials have been initiated to fight the disease. Among those, hydroxychloroquine and azithromycin had initially suggested improve outcomes. Despite any demonstrated beneficial effects, they are still in use some countries but reported prolong QT interval induce life-threatening arrhythmia. Since significant proportion world population may be treated with such COVID-19 therapies, evaluation...
Protoxin II (ProTx II) is a high affinity gating modifier that thought to selectively block the Nav 1.7 voltage-dependent Na+ channel, major therapeutic target for control of pain. We aimed at producing ProTx analogues entitled with novel functionalities cell distribution studies and biochemical characterization its channel targets.We took advantage properties peptide, combined slow off rate, design number new tagged useful imaging biochemistry purposes. used high-throughput automated...
α-bungarotoxin is a large, 74 amino acid toxin containing five disulphide bridges, initially identified in the venom of Bungarus multicinctus snake. Like most large toxins, chemical synthesis challenging, explaining why all previous reports use purified or recombinant α-bungarotoxin. However, only allows easy insertion non-natural acids new functionalities. Herein, we describe procedure for fluorescent-tagged The full-length peptide was designed to include an alkyne function at...
IKr current, a major component of cardiac repolarization, is mediated by human Ether-à-go-go-Related Gene (hERG, Kv11.1) potassium channels. The blockage these channels pharmacological compounds associated to drug-induced long QT syndrome (LQTS), which life-threatening disorder characterized ventricular arrhythmias and defects in repolarization that can be illustrated using cardiomyocytes derived from human-induced pluripotent stem cells (hiPS-CMs). This study was meant assess the...
Mutations in KCNH2 cause long or short QT syndromes (LQTS SQTS) predisposing to life-threatening arrhythmias. Over 1000 hERG variants have been described by clinicians, but most remain be characterised. The objective is standardise and accelerate the phenotyping process contribute clinician diagnosis patient counselling. In silico evaluation was also included characterise structural impact of variants.
The enteric nervous system (ENS) is the intrinsic that innervates entire digestive tract and regulates major functions. Recent evidence has shown functions of ENS critically rely on neuronal connectivity; however, experimental models to decipher underlying mechanisms are limited. Compared central system, for which pure cultures have been developed decades recognized as a reference in field neuroscience, an equivalent model neurons lacking. In this study, we novel highly rat embryonic with...
Controversial reports have suggested that SARS-CoV E and 3a proteins are plasma membrane viroporins. Here, we aimed at better characterizing the cellular responses induced by these proteins. First, show expression of SARS-CoV-2 or protein in CHO cells gives rise to with newly acquired round shapes detach from Petri dish. This suggests cell death is upon protein. We confirmed this using flow cytometry. In adhering expressing protein, whole-cell currents were not different those control,...
Nav1.1 is an important pharmacological target as this voltage-gated sodium channel involved in neurological and cardiac syndromes. Channel activators are actively sought to try compensate for haploinsufficiency several of these pathologies. Herein we used a natural source new peptide compounds active on ion channels screened drugs capable inhibit inactivation way decreased function. We discovered that JzTx-34 highly subsequently performed full structure-activity relationship investigation...