• Amaury François, Niklas Schüetter, Sophie Laffray, Juan Sanguesa, Anne Pizzoccaro, Stefan Dubel, Annabelle Mantilleri, Joel Nargeot, Jacques Noël, John N Wood, Aziz Moqrich, Olaf Pongs, and Emmanuel Bourinet.
• 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.
• Cell Rep. 2015 Jan 20; 10 (3): 370-382.

AbstractThe 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.Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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