Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing

By K. Nagata, A. Duggan, Gagan Kumar, J. García-Añoveros. Journal of Neuroscience, 2005

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Mechanosensory channels of sensory cells mediate the sensations of hearing, touch, and some forms of pain. The TRPA1 (a member of the TRP family of ion channel proteins) channel is activated by pain-producing chemicals, and its inhibition impairs hair cell mechanotransduction. As shown here and previously, TRPA1 is expressed by hair cells as well as by most nociceptors (small neurons of dorsal root, trigeminal, and nodose ganglia) and localizes to their sensory terminals (mechanosensory stereocilia and peripheral free nerves, respectively). Thus, TRPA1 channels are proposed to mediate transduction in both hair cells and nociceptors. Accordingly, we find that heterologously expressed TRPA1 display channel behaviors expected for both auditory and nociceptive transducers. First, TRPA1 and the hair cell transducer share a unique set of pore properties not described for any other channel (block by gadolinium, amiloride, gentamicin, and ruthenium red, a ranging conductance of ∼100 pS that is reduced to 54% by calcium, permeating calcium-induced potentiation followed by closure, and reopening by depolarization), supporting a direct role of TRPA1 as a pore-forming subunit of the hair cell transducer. Second, TRPA1 channels inactivate in hyperpolarized cells but remain open in depolarized cells. This property provides a mechanism for the lack of desensitization, coincidence detection, and allodynia that characterize pain by allowing a sensory neuron to respond constantly to sustained stimulation that is suprathreshold (i.e., noxious) and yet permitting the same cell to ignore sustained stimulation that is subthreshold (i.e., innocuous). Our results support a TRPA1 role in both nociceptor and hair cell transduction.

Subfields: Cellular and Molecular Neuroscience, Sensory Systems

View Paper: https://www.semanticscholar.org/paper/cb68bbd3c6156a0dbec86c1cc99c4254fa9e5101

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Citations in the corpus

Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with aδ/c‐fibers and colocalization with trk receptors (2005, background): “Similar values have also been obtained from mild cooling (7–15°C) in rat trigeminal ganglion neurons (Nealen et al., 2003) and in mouse ganglia (McKemy et al., 2002; Viana et al., 2002).”
Transient Receptor Potential A1 Is a Sensory Receptor for Multiple Products of Oxidative Stress (2008, neutral): “A similar waveform and calcium dependence of TRPA1 mediated currents has been noted with either AITC or cinnamaldehyde as the agonist (Nagata et al., 2005; Doerner et al., 2007).”
An introduction to TRP channels. (2006, background): “But TRPA1 also exhibits unique properties: It has been tentatively identified as the elusive hearing transduction channel (169, 170).”
Cellular and Molecular Mechanisms of Pain (2009, neutral): “However, there continues to be disagreement as to whether native or recombinant TRPA1 is intrinsically cold sensitive (Bandell et al., 2004; Jordt et al., 2004; Karashima et al., 2009; Nagata et al., 2005; Zurborg et al., 2007).”
Trp ion channels and temperature sensation. (2006, background): “Two independent groups, while reporting activation of TRPA1 by mustard oil, did not see cold-mediated activation of TRPA1 in heterologous expression systems ( Jordt et al. 2004, Nagata et al. 2005).”
TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. (2006, neutral): “Indeed, this is consistent with more recent studies examining the expression of TRPA1 in trigeminal or dorsal root ganglia using histological methods (Bautista et al., 2005; Kobayashi et al., 2005; Nagata et al., 2005).”
TRP channels and pain. (2013, background): “Both aspects of regulation can be observed when calcium is supplied to the intracellular face of cell-free excised membrane patches, which suggests that calcium exerts its effects on TRPA1 by interacting directly with an intracellular domain(s) of the channel (Nagata et al. 2005, Wang et al. 2008).”
TRP Channels (2012, neutral): “TRPA1 has been questioned by some later studies 169, 194, 288, 519), most researchers now agree that can be directly gated by cold temperatures (Fig.”