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

Authors: Amaury Francois, Niklas Schüetter, Sophie Laffray, Juan Sanguesa, Anne Pizzoccaro, Stefan Dübel, Annabelle Mantilleri, Joel Nargeot, Jacques Noël, John N Wood, Aziz Moqrich, Olaf Pongs, Emmanuel Bourinet

Journal, date & volume: Cell Rep, 2015 Jan 14 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25600872

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.