title: The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function.
abstract: The T-type calcium channel Cav3.2 emerges as a key regulator of sensory functions, but its expression pattern within primary afferent neurons and its contribution to modality-specific signaling remain obscure. Here, we elucidate this issue using a unique knockin/flox mouse strain wherein Cav3.2 is replaced by a functional Cav3.2-surface-ecliptic GFP fusion. We demonstrate that Cav3.2 is a selective marker of two major low-threshold mechanoreceptors (LTMRs), Aδ- and C-LTMRs, innervating the most abundant skin hair follicles. The presence of Cav3.2 along LTMR-fiber trajectories is consistent with critical roles at multiple sites, setting their strong excitability. Strikingly, the C-LTMR-specific knockout uncovers that Cav3.2 regulates light-touch perception and noxious mechanical cold and chemical sensations and is essential to build up that debilitates allodynic symptoms of neuropathic pain, a mechanism thought to be entirely A-LTMR specific. Collectively, our findings support a fundamental role for Cav3.2 in touch/pain pathophysiology, validating their critic pharmacological relevance to relieve mechanical and cold allodynia.
authors.affiliation: Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France; CNRS UMR5203, 34095 Montpellier, France; INSERM, U661, 34095 Montpellier, France; Université de Montpellier, 34095 Montpellier, France.
authors.forename: Amaury
authors.initials: A
authors.lastname: François
authors.affiliation: Department of Physiology, University of Saarland, School of Medicine, Kirrberger Straße 1, 66424 Homburg, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Schüetter
authors.affiliation: Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France; CNRS UMR5203, 34095 Montpellier, France; INSERM, U661, 34095 Montpellier, France; Université de Montpellier, 34095 Montpellier, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Laffray
authors.affiliation: Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France; CNRS UMR5203, 34095 Montpellier, France; INSERM, U661, 34095 Montpellier, France; Université de Montpellier, 34095 Montpellier, France.
authors.forename: Juan
authors.initials: J
authors.lastname: Sanguesa
authors.affiliation: Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France; CNRS UMR5203, 34095 Montpellier, France; INSERM, U661, 34095 Montpellier, France; Université de Montpellier, 34095 Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Pizzoccaro
authors.affiliation: Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France; CNRS UMR5203, 34095 Montpellier, France; INSERM, U661, 34095 Montpellier, France; Université de Montpellier, 34095 Montpellier, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dubel
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, 13288 Marseille, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Mantilleri
authors.affiliation: Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France; CNRS UMR5203, 34095 Montpellier, France; INSERM, U661, 34095 Montpellier, France; Université de Montpellier, 34095 Montpellier, France.
authors.forename: Joel
authors.initials: J
authors.lastname: Nargeot
authors.affiliation: Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France; Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 CNRS, 660 route des lucioles, 06560 Valbonne, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Noël
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: John N
authors.initials: JN
authors.lastname: Wood
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, 13288 Marseille, France.
authors.forename: Aziz
authors.initials: A
authors.lastname: Moqrich
authors.affiliation: Department of Physiology, University of Saarland, School of Medicine, Kirrberger Straße 1, 66424 Homburg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Pongs
authors.affiliation: Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France; CNRS UMR5203, 34095 Montpellier, France; INSERM, U661, 34095 Montpellier, France; Université de Montpellier, 34095 Montpellier, France. Electronic address: emmanuel.bourinet@igf.cnrs.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourinet