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Cell Rep. 2015 Jan 20;10(3):370-382. doi: 10.1016/j.celrep.2014.12.042. Epub 2015 Jan 15.

The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function.

Author information

1
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.
2
Department of Physiology, University of Saarland, School of Medicine, Kirrberger Straße 1, 66424 Homburg, Germany.
3
Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, 13288 Marseille, France.
4
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.
5
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.
6
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.

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.

PMID:
25600872
DOI:
10.1016/j.celrep.2014.12.042
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