Cell Reports
Volume 10, Issue 3, 20 January 2015, Pages 370-382
Journal home page for Cell Reports

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

https://doi.org/10.1016/j.celrep.2014.12.042Get rights and content
Under a Creative Commons license
open access

Highlights

  • Cav3.2 calcium channels are markers of both C- and Aδ- low-threshold mechanoreceptors

  • Cav3.2 in receptive fields and axons facilitates action potential initiation and conduction

  • Cav3.2 in C-LTMR governs innocuous touch, noxious mechanical cold, and chemical pain

  • Cav3.2 channels in C-LTMRs are molecular substrates of allodynia in neuropathic pain

Summary

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.

Cited by (0)

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).