Article
Allergy
Nicolas Giang, Marion Mars, Marc Moreau, Jose E. Mejia, Gregory Bouchaud, Antoine Magnan, Marine Michelet, Brice Ronsin, Geoffrey G. Murphy, Joerg Striessnig, Jean-Charles Guery, Lucette Pelletier, Magali Savignac
Summary: This study demonstrates that Ca(v)1.2 and Ca(v)1.3 in Th2 cells have non-redundant and synergistic functions, and deficiency in either one of these channels is sufficient to inhibit cardinal features of type 2 airway inflammation.
Article
Multidisciplinary Sciences
Taylor L. Voelker, Silvia G. del Villar, Maartje Westhoff, Alexandre D. Costa, Andrea M. Coleman, Johannes W. Hell, Mary C. Horne, Eamonn J. Dickson, Rose E. Dixon
Summary: CaV1.2 channels in the heart are affected by angiotensin II, a therapeutic target of heart failure drugs and regulator of blood pressure. Angiotensin II causes a decrease in PIP2, which leads to the suppression of CaV1.2 currents. This study found that PIP2 depletion destabilizes CaV1.2 channels and reduces their expression and function. The results suggest that PIP2 plays a crucial role in maintaining cardiac excitability and that angiotensin II-induced PIP2 depletion impairs excitation-contraction coupling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cardiac & Cardiovascular Systems
Arianne Papa, Jared Kushner, Jessica A. Hennessey, Alexander N. Katchman, Sergey Zakharov, Bi-xing Chen, Lin Yang, Ree Lu, Stephen Leong, Johanna Diaz, Guoxia Liu, Daniel Roybal, Xianghai Liao, Pedro J. del Rivero Morfin, Henry M. Colecraft, Geoffrey S. Pitt, Oliver Clarke, Veli Topkara, Manu Ben-Johny, Steven O. Marx
Summary: The study identified that the activity of Ca(V)1.2 channels is dynamically modulated by factors converging at the alpha(1C) I-II loop under different conditions, including basal conditions, beta-adrenergic stimulation, and heart failure. This has significant implications for cardiac physiology and pathophysiology.
CIRCULATION RESEARCH
(2021)
Article
Biology
Kwun Nok Mimi Man, Peter Bartels, Peter B. Henderson, Karam Kim, Mei Shi, Mingxu Zhang, Sheng-Yang Ho, Madeline Nieves-Cintron, Manuel F. Navedo, Mary C. Horne, Johannes W. Hell
Summary: The cellular mechanisms by which norepinephrine regulates behaviors in the brain remain unknown. This study identifies the L-type Ca2+ channel Ca(V)1.2 as a major target for alpha(1)-adrenergic receptors (ARs) in the hippocampus. Activation of alpha(1)AR signaling enhances LTCC activity through the PKC-Pyk2-Src pathway, suggesting that Ca(V)1.2 is a central conduit for norepinephrine signaling. Inhibition of Pyk2 and Src blocks hippocampal long-term potentiation (LTP), indicating that the enhancement of Ca(V)1.2 activity through alpha(1)AR-Pyk2-Src signaling regulates synaptic strength.
Article
Cell Biology
Rachel Conrad, Daniel Kortzak, Gustavo A. Guzman, Erick Miranda-Laferte, Patricia Hidalgo
Summary: Membrane depolarization activates the Ca(V)1.2 L-type calcium channel, leading to various excitation coupling responses. The presence of Ca-V beta promotes fast transport speed along anterograde trafficking and controls the endocytic turnover of L-type calcium channels.
Review
Biochemistry & Molecular Biology
Maartje Westhoff, Rose E. Dixon
Summary: During cardiac excitation-contraction coupling, the activity of Ca(V)1.2 channels plays a crucial role in regulating calcium influx, intracellular calcium concentration, and ultimately myocardial contraction. Recent studies have identified internal reservoirs of preformed Ca(V)1.2 channels that can be rapidly mobilized during acute stress to enhance sarcolemmal expression and maintain cardiac function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Amber E. Plante, Joshua P. Whitt, Andrea L. Meredith
Summary: Circadian rhythms in mammals are timed by the SCN through the regulation of membrane currents, such as BK and LTCC currents. LTCCs and RyRs contribute to the baseline membrane potential and the action potential-evoked BK current in SCN during the day and night, respectively. Specific partnerships between BK channels and Ca(V)1.3 channels optimize the subthreshold BK current activation critical for firing rate regulation.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Cell Biology
Joerg Isensee, Marianne van Cann, Patrick Despang, Dioneia Araldi, Katharina Moeller, Jonas Petersen, Achim Schmidtko, Jan Matthes, Jon D. Levine, Tim Hucho
Summary: Depolarization activates protein kinase A type II in nociceptive neurons, leading to sensitization. This process involves calcium influx through Ca(V)1.2 channels, calpains modulation, and phosphorylation of Ca(V)1.2, ultimately resulting in local peripheral hyperalgesia.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Physiology
Sahil Zaveri, Ujala Srivastava, Yongxia Sarah Qu, Mohamed Chahine, Mohamed Boutjdir
Summary: Ca2+ plays a crucial role in excitation-contraction coupling in cardiac myocytes, and dysfunctional Ca2+ regulation can lead to altered contraction force and cardiac arrhythmias. The entry of Ca2+ into cardiomyocytes is mainly mediated by L-type Ca2+ channels, with Ca(v)1.3 being implicated in sinoatrial and atrioventricular node dysfunction as well as atrial fibrillation. Understanding the functional and molecular pathways of Ca(v)1.3 in the heart may help develop targeted therapeutic interventions for these arrhythmias.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qian Yang, Tyler L. L. Perfitt, Juliana Quay, Lan Hu, Dorian Lawson-Qureshi, Roger J. J. Colbran
Summary: The clustering of LTCCs in the plasma membrane is important for highly localized Ca2+ signaling. Shank3, a scaffolding protein, interacts with Ca(V)1.3 calcium channel and promotes LTCC-dependent excitation-transcription coupling. The formation of Ca(V)1.3 LTCC complexes is facilitated by Ca-V beta subunits and is disrupted by increased Ca2+ concentration.
JOURNAL OF NEUROCHEMISTRY
(2023)
Editorial Material
Physiology
Laurent Ferron, Gerald W. Zamponi
Summary: The specific gating effects of Timothy syndrome Ca(V)1.2 channel mutations determine the deficits in cardiovascular and nervous systems.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Ludovica Filippini, Nadine J. J. Ortner, Teresa Kaserer, Jorg Striessnig
Summary: Voltage-gated L-type Ca2+-channels, especially Ca(v)1.3 subtype, are potential drug targets for the treatment of various diseases. However, the selectivity of Ca(v)1.3-selective blockers remains controversial, and there are no suitable pharmacological tools to confirm or refute the role of Ca(v)1.3 channels in cellular responses. Essential criteria for a small molecule to be considered Ca(v)1.3-selective are suggested.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Guillermo Avila
Summary: Fluorofenidone (AKF-PD) is a compound that inhibits fibrosis and inflammation. It has been shown to enhance cell contractility and Ca2+ channel activity in cardiac myocytes, suggesting potential therapeutic effects for cardiac diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Wen-Wen Zhang, Hong Cao, Yang Li, Xian-Jun Fu, Yu-Qiu Zhang
Summary: This study reveals the important role of peripheral adenylyl cyclase isoform AC3 in nociceptive transmission and regulation of opioid receptor signaling. The conditional knockout of AC3 in mouse DRGs led to increased nociceptive responses, decreased Kv channel currents, and increased neuronal excitability. Furthermore, AC3 knockout abolished the analgesic effect of KOR agonist and its inhibition on Kv channel, suggesting the involvement of AC3 in KOR opioid analgesia through classical G alpha(i/o) signaling or direct interaction with KOR. Additionally, the upregulation of AC1 and cAMP levels in AC3-deficient DRGs highlights the compensatory role of AC1 in the absence of AC3.
Article
Chemistry, Multidisciplinary
Hui Wang, Mingqi Xie, Giorgio Rizzi, Xin Li, Kelly Tan, Martin Fussenegger
Summary: Parkinson's disease (PD) is primarily caused by excessive activity-related Ca2+ oscillations, resulting in the selective loss of substantia nigra dopaminergic neurons. In this study, a synthetic-biology-inspired drug-discovery platform was used to identify potential PD drugs. Through virtual screening and deep-learning neural networks, the compound sclareol was identified as a promising candidate for PD pharmacotherapy. In vitro and in vivo experiments confirmed that sclareol selectively inhibits Ca(v)1.3, reduces the firing response of SNc DA neurons, and protects against DA neuronal loss and motor impairment in a mouse model of PD.
Article
Biochemical Research Methods
Cynthia Abboud, Alexia Duveau, Rabia Bouali-Benazzouz, Karine Masse, Joseph Mattar, Louison Brochoire, Pascal Fossat, Eric Boue-Grabot, Walid Hleihel, Marc Landry
Summary: Chronic pain is a major health problem and studying animal models that recapitulate diverse pain symptoms is crucial for understanding pain mechanisms. These models reproduce different pain phenotypes, allowing for examination of multidimensional aspects of pain and providing insights into the cellular and molecular basis of pain conditions. The validity of these models is based on their ability to mimic human diseases and predict treatment outcomes.
JOURNAL OF NEUROSCIENCE METHODS
(2021)
Review
Neurosciences
Rabia Bouali-Benazzouz, Marc Landry, Abdelhamid Benazzouz, Pascal Fossat
Summary: Animal models play a crucial role in studying neuropathic pain, but objective assessment of pain and validating pain phenotypes present challenges. Utilizing various behavioral approaches to investigate and validate pain phenotypes can help uncover novel pain mechanisms.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Neurosciences
Maria Isabel Carreno-Munoz, Maria Carmen Medrano, Arnaldo Ferreira Gomes Da Silva, Christian Gestreau, Clement Menuet, Thomas Leinekugel, Maelys Bompart, Fabienne Martins, Enejda Subashi, Franck Aby, Andreas Frick, Marc Landry, Manuel Grana, Xavier Leinekugel
Summary: The newly developed behavioral phenotyping device utilizes sensitive sensors and video analysis techniques to capture minute movements and behavioral signals of animals, providing detailed access to previously overlooked components of behavior.
NEUROPSYCHOPHARMACOLOGY
(2022)
Review
Anesthesiology
Mohamed G. Sobeeh, Sherief Ghozy, Rami M. Elshazli, Marc Landry
Summary: This systematic review found that patients with carpal tunnel syndrome (CTS) exhibit sensory loss, increased thermal and mechanical pain sensitivity, and impaired conditioned pain modulation. However, the evidence for central sensitization in CTS remains inconclusive.
Article
Biochemistry & Molecular Biology
Sandra Dubes, Anais Soula, Sebastien Benquet, Beatrice Tessier, Christel Poujol, Alexandre Favereaux, Olivier Thoumine, Mathieu Letellier
Summary: This study reveals the molecular mechanism of synapse-specific homeostatic plasticity. The synaptic tagging mechanism, driven by synaptopodin, regulates the enhancement of synaptic strength in a synapse-specific manner. This finding shifts the understanding of homeostatic plasticity towards the idea that the ability for changes depends on the functional and biochemical state of individual synapses.
Article
Multidisciplinary Sciences
Otmane Bouchatta, Franck Aby, Wahiba Sifeddine, Rabia Bouali-Benazzouz, Louison Brochoire, Houria Manouze, Pascal Fossat, Saadia Ba M'Hamed, Mohamed Bennis, Marc Landry
Summary: Clinical evidence suggests that pain hypersensitivity develops in patients with attention-deficit/hyperactivity disorder (ADHD). In this mouse model study, 6-OHDA mice exhibited increased sensitization to thermal and mechanical stimuli, as well as amplified sensitivity to pathological inflammatory stimulus compared to control mice. The study also found that ADHD-related hyperactivity and anxiety, but not inattention and impulsivity, worsened in the presence of persistent inflammatory conditions. The research discovered that hyperactivity in the anterior cingulate cortex (ACC) altered the ACC-posterior insula circuit and triggered changes in spinal networks that underlie nociceptive sensitization.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Guillaume Beucher, Marie-Lise Blondot, Alexis Celle, Noemie Pied, Patricia Recordon-Pinson, Pauline Esteves, Muriel Faure, Mathieu Metifiot, Sabrina Lacomme, Denis Dacheux, Derrick R. Robinson, Gernot Langst, Fabien Beaufils, Marie-Edith Lafon, Patrick Berger, Marc Landry, Denis Malvy, Thomas Trian, Marie-Line Andreola, Harald Wodrich
Summary: This study found that SARS-CoV-2 infection starts in bronchial epithelial cells from adult donors and spreads throughout the epithelium within 24 to 48 hours. Syncytia formation contributes to virus propagation. Epithelial cells from child donors have higher resistance to virus infection, which is associated with an accelerated release of type III interferon. The inflammatory response is attenuated in children. These findings may explain the age-related susceptibility to COVID-19 based on epidemiological observations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Damien Huzard, Miquel Martin, Francois Maingret, Jean Chemin, Freddy Jeanneteau, Pierre-Francois Mery, Pascal Fossat, Emmanuel Bourinet, Amaury Francois
Summary: C-LTMRs play a crucial role in feeling touch and social behaviors. Functional deficiency of C-LTMRs leads to social isolation, while transient increase in C-LTMR excitability is beneficial for social interactions and has prosocial influences.
Article
Multidisciplinary Sciences
Franck Aby, Louis-Etienne Lorenzo, Zoe Grivet, Rabia Bouali-Benazzouz, Hugo Martin, Stephane Valerio, Sara Whitestone, Dominique Isabel, Walid Idi, Otmane Bouchatta, Philippe De Deurwaerdere, Antoine G. Godin, Cyril Herry, Xavier Fioramonti, Marc Landry, Yves De Koninck, Pascal Fossat
Summary: Research has shown that serotonin (5-HT) neurons have a pain-relieving effect in mice who have not experienced pain before, but become pain-promoting in neuropathic pain models. An imbalance in spinal KCC2 function turns this pain relief into pain promotion, but KCC2 enhancers can restore the pain-relieving effect. Additionally, combining selective serotonin reuptake inhibitors (SSRIs) with KCC2 enhancers can effectively relieve pain hypersensitivity caused by nerve injury.
Article
Biology
Morgane Le Bon-Jego, Marie-Jeanne Cabirol, Daniel Cattaert
Summary: The study shows that synaptic function and spike conduction mechanisms can persist in axons for several months after losing their nucleus. However, the loss of synaptic transmission can be prevented by in vivo sensory nerve stimulation.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2022)
Article
Cell Biology
Maria Meseguer-Beltran, Sandra Sanchez-Sarasua, Marc Landry, Nora Kerekes, Ana Maria Sanchez-Perez
Summary: This study aimed to demonstrate the association between dopaminergic deficit and neuroinflammation in ADHD symptoms. ADHD mice model was used and treated with an anti-inflammatory phytohormone ABA. The results showed that female mice with dopaminergic deficit had increased pain sensitivity, while male mice displayed hyperactivity. These findings provide new clues for potential treatments for ADHD.
Article
Pharmacology & Pharmacy
Wahiba Sifeddine, Saadia Ba-M'hamed, Marc Landry, Mohamed Bennis
Summary: This study investigated the effects of atomoxetine on ADHD-like symptoms and pain hypersensitivity. The results showed that chronic administration of atomoxetine significantly alleviated ADHD symptoms and attenuated pain responses, likely mediated by alpha- and beta-adrenergic and D2/D3 dopaminergic receptors. These findings suggest potential new indications for atomoxetine.
PHARMACOLOGICAL REPORTS
(2023)
Article
Multidisciplinary Sciences
Arnaud Landra-Willm, Ameya Karapurkar, Alexia Duveau, Anne Amandine Chassot, Lucille Esnault, Gerard Callejo, Marion Bied, Stephanie Hafner, Florian Lesage, Brigitte Wdziekonski, Anne Baron, Pascal Fossat, Laurent Marsollier, Xavier Gasull, Eric Boue-Grabot, Michael A. Kienzler, Guillaume Sandoz
Summary: By manipulating neuronal activity using optogenetics and photopharmacology, researchers have developed a light-activatable molecule called LAKI that can block pain-related potassium channels. This molecule has the potential to be a valuable tool for studying these channels, and it can also be used to remotely control pain in animal models without the need for genetic manipulations or viral infection. This non-invasive and reversible approach has applications in pain research and drug screening.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Damien Gilabert, Alexia Duveau, Sara Carracedo, Nathalie Linck, Adeline Langla, Rieko Muramatsu, Friedrich Koch-Nolte, Francois Rassendren, Thomas Grutter, Pascal Fossat, Eric Boue-Grabot, Lauriane Ulmann
Summary: Recent evidence suggests that the P2X4 receptor plays a sex-dependent role in spinal microglia in neuropathic pain development. The increased cell surface expression of P2X4 leads to mechanical hypersensitivity and spinal neuron hyperexcitability in both male and female mice. The upregulation of P2X4 in reactive microglia is crucial for neuropathic pain, and blocking P2X4 or TrkB can alleviate tactile allodynia.