Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing

Keiichi Nagata, Anne Duggan, Gagan Kumar, Jaime García-Añoveros*

*Corresponding author for this work

Research output: Contribution to journalArticle

461 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4052-4061
Number of pages10
JournalJournal of Neuroscience
Volume25
Issue number16
DOIs
StatePublished - Apr 20 2005

Fingerprint

Nociceptors
Transducers
Hearing
Pain
Nodose Ganglion
Stereocilia
Calcium
Ruthenium Red
Trigeminal Ganglion
Amiloride
Hyperalgesia
Gadolinium
Touch
Spinal Ganglia
Sensory Receptor Cells
Gentamicins
Ion Channels
Peripheral Nerves
Neurons

Keywords

  • Adaptation
  • Auditory
  • Channel
  • Cochlea
  • Desensitization
  • Hair cell
  • Mechanosensory
  • Multisensory
  • Nociceptor
  • Nodose
  • Pain
  • Transduction

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{d1c71190e00647efa9089135d3595476,
title = "Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing",
abstract = "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.",
keywords = "Adaptation, Auditory, Channel, Cochlea, Desensitization, Hair cell, Mechanosensory, Multisensory, Nociceptor, Nodose, Pain, Transduction",
author = "Keiichi Nagata and Anne Duggan and Gagan Kumar and Jaime Garc{\'i}a-A{\~n}overos",
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Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. / Nagata, Keiichi; Duggan, Anne; Kumar, Gagan; García-Añoveros, Jaime.

In: Journal of Neuroscience, Vol. 25, No. 16, 20.04.2005, p. 4052-4061.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing

AU - Nagata, Keiichi

AU - Duggan, Anne

AU - Kumar, Gagan

AU - García-Añoveros, Jaime

PY - 2005/4/20

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N2 - 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.

AB - 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.

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KW - Channel

KW - Cochlea

KW - Desensitization

KW - Hair cell

KW - Mechanosensory

KW - Multisensory

KW - Nociceptor

KW - Nodose

KW - Pain

KW - Transduction

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DO - 10.1523/JNEUROSCI.0013-05.2005

M3 - Article

VL - 25

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EP - 4061

JO - Journal of Neuroscience

JF - Journal of Neuroscience

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