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

Authors
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, Emmanuel Bourinet

Lab
Institut de Génomique Fonctionnelle, Université de Montpellier, France

Journal
Cell Reports

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), A?- 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.

BIOSEB Instruments Used:
Cold Hot Plate Test (BIO-CHP)