Faculty Collaboration Database

TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci 2009 Apr 15;29(15):4808-19

Date

04/17/2009

Pubmed ID

19369549

Pubmed Central ID

PMC2744291

DOI

10.1523/JNEUROSCI.5380-08.2009

Scopus ID

2-s2.0-65549123596 (requires institutional sign-in at Scopus site)   261 Citations

Abstract

Transient receptor potential ankyrin 1 (TRPA1) is expressed by nociceptive neurons of the dorsal root ganglia (DRGs) and trigeminal ganglia, but its roles in cold and mechanotransduction are controversial. To determine the contribution of TRPA1 to cold and mechanotransduction in cutaneous primary afferent terminals, we used the ex vivo skin-nerve preparation from Trpa1(+/+), Trpa1(+/-), and Trpa1(-/-) adult mouse littermates. Cutaneous fibers from TRPA1-deficient mice showed no deficits in acute cold sensitivity, but they displayed striking deficits in mechanical response properties. C-fiber nociceptors from Trpa1(-/-) mice exhibited action potential firing rates 50% lower than those in wild-type C-fibers across a wide range of force intensities. Adelta-fiber mechanonociceptors also had reduced firing, but only at high intensity forces (>100 mN). Surprisingly, the firing rates of low-threshold Abeta and D-hair mechanoreceptive fibers were also altered. TRPA1 protein and mRNA expression was assessed in DRG neurons and cutaneous innervation by using Trpa1 in situ hybridization, an antibody for TRPA1, and an antibody for placental alkaline phosphatase (PLAP) in mice in which PLAP was substituted for Trpa1. DRG neurons of all sizes expressed Trpa1 mRNA or PLAP immunoreactivity. TRPA1 or PLAP immunolabeling was detected not only on many thin-caliber axons and intraepidermal endings but also on many large-caliber axons as well as lanceolate and Meissner endings. Epidermal and hair follicle keratinocytes also express TRPA1 message and protein. We propose that TRPA1 modulates mechanotransduction via a cell-autonomous mechanism in nociceptor terminals and possibly through a modulatory role in keratinocytes, which may interact with sensory terminals to modify their mechanical firing properties.

Author List

Kwan KY, Glazer JM, Corey DP, Rice FL, Stucky CL

Author

Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amyloid beta-Peptides
Animals
Cold Temperature
Ganglia, Spinal
Male
Mechanotransduction, Cellular
Mice
Mice, Knockout
Mice, Transgenic
Nociceptors
Physical Stimulation
Sensory Receptor Cells
Skin
TRPA1 Cation Channel
Transient Receptor Potential Channels