A5090477325- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- Migraine and Headache Studies
- Nicotinic Acetylcholine Receptors Study
- Neuroscience of respiration and sleep
- Ion Channels and Receptors
- Blood properties and coagulation
- Ion Transport and Channel Regulation
- Nitric Oxide and Endothelin Effects
- Pain Mechanisms and Treatments
- Vagus Nerve Stimulation Research
- Connexins and lens biology
- Lipid Membrane Structure and Behavior
- Advanced Chemical Sensor Technologies
- Venomous Animal Envenomation and Studies
- Cardiac electrophysiology and arrhythmias
- Hemoglobin structure and function
University Medical Center Hamburg-Eppendorf
2022-2024
Universität Hamburg
2022-2024
Institut de Pharmacologie Moléculaire et Cellulaire
2018-2022
Laboratoire d'Excellence Canaux Ioniques d'Intérêt Thérapeutique
2018-2022
Université Côte d'Azur
2018-2022
Centre National de la Recherche Scientifique
2018-2022
Inserm
2021
Centre Hospitalier Universitaire de Nice
2021
Fédération Hospitalo-Universitaire, Paris Center for Microbiome Medicine
2021
Heidelberg University
2021
A central question in mechanobiology is how mechanical forces acting or on cells are transmitted to mechanically-gated PIEZO channels that convert these into biochemical signals. Here we examined the role of intracellular domains PIEZO2, which account for 25% channel, and demonstrate fine-tune properties such as poking stretch-sensitivity, velocity coding single channel conductance. Moreover, show intrinsically disordered linker between transmembrane helices twelve thirteen (IDR5) required...
Acid-sensing ion channels (ASICs) are neuronal proton sensors emerging as potential therapeutic targets in pain of the orofacial region. Amiloride, a non-specific ASIC blocker, has been shown to exert beneficial effects animal models migraine and patients. We explored involvement ASIC1-subtype cutaneous allodynia, hallmark affecting cephalic extra-cephalic regions about 70% migrainers.We investigated systemic injections amiloride mambalgin-1, specific inhibitor ASIC1a- ASIC1b-containing...
Activation and sensitization of trigeminal ganglia (TG) sensory neurons, leading to the release pro-inflammatory peptides such as calcitonin gene-related peptide (CGRP), are likely a key component in migraine-related headache induction. Reducing TG neuron excitability represents therefore an attractive alternative strategy relieve migraine pain. Here by using pharmacology genetic invalidation ex vivo vivo, we demonstrate that activating TREK1 TREK2 two-pore-domain potassium (K2P) channels...
PKA is a downstream effector of many inflammatory mediators that induce pain hypersensitivity by increasing the mechanosensitivity nociceptive sensory afferent. Here, we examine molecular mechanism underlying PKA-dependent modulation mechanically activated ion channel PIEZO2, which confers to nociceptors. Using phosphorylation site prediction algorithms, identified multiple putative and highly conserved sites located on intracellular intrinsically disordered regions PIEZO2. Site-directed...
Abstract Mechanically silent nociceptors are sensory afferents that insensitive to noxious mechanical stimuli under normal conditions but become sensitized such during inflammation. Using RNA-sequencing and quantitative RT-PCR we demonstrate inflammation upregulates the expression of transmembrane protein TMEM100 in electrophysiology revealed over-expression is required sufficient un-silence mice. Moreover, show mice lacking do not develop secondary hypersensitivity—i.e., pain...
Neuronal proton-gated acid-sensing ion channels (ASICs) participate in the detection of tissue acidosis, a phenomenon often encountered painful pathologic diseases. Such conditions involve parallel activation various signaling pathways such as mitogen activated protein kinases (MAPKs) that ultimately leads to phenotype modifications sensory neurons. Here, we identify one member MAPKs, c-Jun N-terminal kinase (JNK), new post-translational positive regulator ASICs rodent Recombinant H +...
Summary Silent nociceptors are sensory afferents that insensitive to noxious mechanical stimuli under normal conditions but become sensitized such during inflammation. Using RNA-sequencing and quantitative RT-PCR we demonstrate inflammation selectively upregulates the expression of transmembrane protein TMEM100 in silent electrophysiology revealed over-expression is required sufficient un-silence nociceptors. Moreover, show mice lacking do not develop secondary allodynia – i.e. pain...
Abstract The mechanically activated ion channel PIEZO1 confers mechanosensitivity to many cell types and is thus essential for numerous physiological processes triggered by mechanical cues 1–4 . channels assemble as propeller-shaped trimers 5–7 , which supposedly undergo a transition from curved conformational state into flattened upon activation 8–11 Whether this gating model also applies clusters what extent membrane curvature alters conformation in living cells, is, however, still...
Abstract A central question in mechanobiology is how mechanical forces acting or on a cell are transmitted to mechanically-gated PIEZO channels that convert these into biochemical signals. Here we show PIEZO2 sensitive force-transmission via the membrane (force-from-lipids) as well force transmission cytoskeleton (force-from-filament) and demonstrate latter requires intracellular linker between transmembrane helices nine ten (IDR5). Moreover, rendering insensitive force-from-filament by...
Activation and sensitization of trigeminal (TG) ganglia sensory neurons, leading to the release pro-inflammatory peptides such as calcitonin gene-related peptide (CGRP), are likely a key component in migraine-related headache induction. Reducing TG neuron excitability represents therefore an attractive alternative strategy relieve migraine pain. Here by using pharmacology genetic invalidation ex vivo vivo, we demonstrate that activating TREK1- TREK2- Two-Pore-Domain potassium ( K 2P )...
Abstract Neuronal proton-gated Acid-Sensing Ion Channels (ASICs) participate in the detection of tissue acidosis, a phenomenon often encountered painful pathological diseases. Such conditions involve parallel activation various signaling pathways such as Mitogen Activated Protein Kinases (MAPKs) that ultimately leads to phenotype modifications sensory neurons. Here, we identify one member MAPKs, c-Jun N-terminal Kinase (JNK), new post-translational positive regulator ASIC channels rodent...