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Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing
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| Zeitschriftentitel: | The Journal of Neuroscience |
|---|---|
| Personen und Körperschaften: | , , , |
| In: | The Journal of Neuroscience, 25, 2005, 16, S. 4052-4061 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
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| Schlagwörter: |
| author_facet |
Nagata, Keiichi Duggan, Anne Kumar, Gagan García-Añoveros, Jaime Nagata, Keiichi Duggan, Anne Kumar, Gagan García-Añoveros, Jaime |
|---|---|
| author |
Nagata, Keiichi Duggan, Anne Kumar, Gagan García-Añoveros, Jaime |
| spellingShingle |
Nagata, Keiichi Duggan, Anne Kumar, Gagan García-Añoveros, Jaime The Journal of Neuroscience Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing General Neuroscience |
| author_sort |
nagata, keiichi |
| spelling |
Nagata, Keiichi Duggan, Anne Kumar, Gagan García-Añoveros, Jaime 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.0013-05.2005 <jats:p>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.</jats:p> Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing The Journal of Neuroscience |
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| title |
Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_unstemmed |
Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_full |
Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_fullStr |
Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_full_unstemmed |
Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_short |
Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_sort |
nociceptor and hair cell transducer properties of trpa1, a channel for pain and hearing |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.0013-05.2005 |
| publishDate |
2005 |
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4052-4061 |
| description |
<jats:p>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.</jats:p> |
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| author | Nagata, Keiichi, Duggan, Anne, Kumar, Gagan, García-Añoveros, Jaime |
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| description | <jats:p>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.</jats:p> |
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| imprint_str_mv | Society for Neuroscience, 2005 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
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| spelling | Nagata, Keiichi Duggan, Anne Kumar, Gagan García-Añoveros, Jaime 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.0013-05.2005 <jats:p>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.</jats:p> Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing The Journal of Neuroscience |
| spellingShingle | Nagata, Keiichi, Duggan, Anne, Kumar, Gagan, García-Añoveros, Jaime, The Journal of Neuroscience, Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing, General Neuroscience |
| title | Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_full | Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_fullStr | Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_full_unstemmed | Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_short | Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| title_sort | nociceptor and hair cell transducer properties of trpa1, a channel for pain and hearing |
| title_unstemmed | Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.0013-05.2005 |