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TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons. J Neurophysiol 2012 Feb;107(3):913-22

Date

11/11/2011

Pubmed ID

22072513

Pubmed Central ID

PMC3289471

DOI

10.1152/jn.00658.2011

Scopus ID

2-s2.0-84855837580 (requires institutional sign-in at Scopus site)   69 Citations

Abstract

The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. However, its role in the mechanical sensitivity of these neurons is unclear. Here, we investigated TRPC1-dependent responses to both innocuous and noxious mechanical force. Mechanically evoked action potentials in cutaneous myelinated A-fiber and unmyelinated C-fiber neurons were quantified using the ex vivo skin-nerve preparation to record from the saphenous nerve, which terminates in the dorsal hairy skin of the hindpaw. Our data reveal that in TRPC1-deficient mice, mechanically evoked action potentials were decreased by nearly 50% in slowly adapting Aβ-fibers, which largely innervate Merkel cells, and in rapidly adapting Aδ-Down-hair afferent fibers compared with wild-type controls. In contrast, differences were not found in slowly adapting Aδ-mechanoreceptors or unmyelinated C-fibers, which primarily respond to nociceptive stimuli. These results suggest that TRPC1 may be important in the detection of innocuous mechanical force. We concurrently investigated the role of TRPC1 in behavioral responses to mechanical force to the plantar hindpaw skin. For innocuous stimuli, we developed a novel light stroke assay using a "puffed out" cotton swab. Additionally, we used repeated light, presumably innocuous punctate stimuli with a low threshold von Frey filament (0.68 mN). In agreement with our electrophysiological data in light-touch afferents, TRPC1-deficient mice exhibited nearly a 50% decrease in behavioral responses to both the light-stroke and light punctate mechanical assays when compared with wild-type controls. In contrast, TRPC1-deficient mice exhibited normal paw withdrawal response to more intense mechanical stimuli that are typically considered measures of nociceptive behavior.

Author List

Garrison SR, Dietrich A, 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

Animals
Evoked Potentials
Female
Male
Mechanoreceptors
Merkel Cells
Mice
Mice, Inbred C57BL
Nerve Fibers, Myelinated
Nerve Fibers, Unmyelinated
Physical Stimulation
Sensory Receptor Cells
Sensory Thresholds
Skin
Skin Physiological Phenomena
TRPC Cation Channels
Touch