Pore dilation occurs in TRPA1 but not in TRPM8 channels
<p>Abstract</p> <p>Abundantly expressed in pain-sensing neurons, TRPV1, TRPA1 and TRPM8 are major cellular sensors of thermal, chemical and mechanical stimuli. The function of these ion channels has been attributed to their selective permeation of small cations (e.g., Ca<sup>...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2009-01-01
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| Series: | Molecular Pain |
| Online Access: | http://www.molecularpain.com/content/5/1/3 |
| _version_ | 1818498587576762368 |
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| author | Faltynek Connie R Cavanaugh Eric J Bianchi Bruce R Kim Donghee Chen Jun Kym Philip R Reilly Regina M |
| author_facet | Faltynek Connie R Cavanaugh Eric J Bianchi Bruce R Kim Donghee Chen Jun Kym Philip R Reilly Regina M |
| author_sort | Faltynek Connie R |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Abundantly expressed in pain-sensing neurons, TRPV1, TRPA1 and TRPM8 are major cellular sensors of thermal, chemical and mechanical stimuli. The function of these ion channels has been attributed to their selective permeation of small cations (e.g., Ca<sup>2+</sup>, Na<sup>+ </sup>and K<sup>+</sup>), and the ion selectivity has been assumed to be an invariant fingerprint to a given channel. However, for TRPV1, the notion of invariant ion selectivity has been revised recently. When activated, TRPV1 undergoes time and agonist-dependent pore dilation, allowing permeation of large organic cations such as Yo-Pro and NMDG<sup>+</sup>. The pore dilation is of physiological importance, and has been exploited to specifically silence TRPV1-positive sensory neurons. It is unknown whether TRPA1 and TRPM8 undergo pore dilation. Here we show that TRPA1 activation by reactive or non-reactive agonists induces Yo-Pro uptake, which can be blocked by TRPA1 antagonists. In outside-out patch recordings using NMDG<sup>+ </sup>as the sole external cation and Na<sup>+ </sup>as the internal cation, TRPA1 activation results in dynamic changes in permeability to NMDG<sup>+</sup>. In contrast, TRPM8 activation does not produce either Yo-Pro uptake or significant change in ion selectivity. Hence, pore dilation occurs in TRPA1, but not in TRPM8 channels.</p> |
| first_indexed | 2024-12-10T20:17:38Z |
| format | Article |
| id | doaj.art-844620bcb9664993bc1d7422844ebcad |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-12-10T20:17:38Z |
| publishDate | 2009-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-844620bcb9664993bc1d7422844ebcad2022-12-22T01:35:09ZengSAGE PublishingMolecular Pain1744-80692009-01-0151310.1186/1744-8069-5-3Pore dilation occurs in TRPA1 but not in TRPM8 channelsFaltynek Connie RCavanaugh Eric JBianchi Bruce RKim DongheeChen JunKym Philip RReilly Regina M<p>Abstract</p> <p>Abundantly expressed in pain-sensing neurons, TRPV1, TRPA1 and TRPM8 are major cellular sensors of thermal, chemical and mechanical stimuli. The function of these ion channels has been attributed to their selective permeation of small cations (e.g., Ca<sup>2+</sup>, Na<sup>+ </sup>and K<sup>+</sup>), and the ion selectivity has been assumed to be an invariant fingerprint to a given channel. However, for TRPV1, the notion of invariant ion selectivity has been revised recently. When activated, TRPV1 undergoes time and agonist-dependent pore dilation, allowing permeation of large organic cations such as Yo-Pro and NMDG<sup>+</sup>. The pore dilation is of physiological importance, and has been exploited to specifically silence TRPV1-positive sensory neurons. It is unknown whether TRPA1 and TRPM8 undergo pore dilation. Here we show that TRPA1 activation by reactive or non-reactive agonists induces Yo-Pro uptake, which can be blocked by TRPA1 antagonists. In outside-out patch recordings using NMDG<sup>+ </sup>as the sole external cation and Na<sup>+ </sup>as the internal cation, TRPA1 activation results in dynamic changes in permeability to NMDG<sup>+</sup>. In contrast, TRPM8 activation does not produce either Yo-Pro uptake or significant change in ion selectivity. Hence, pore dilation occurs in TRPA1, but not in TRPM8 channels.</p>http://www.molecularpain.com/content/5/1/3 |
| spellingShingle | Faltynek Connie R Cavanaugh Eric J Bianchi Bruce R Kim Donghee Chen Jun Kym Philip R Reilly Regina M Pore dilation occurs in TRPA1 but not in TRPM8 channels Molecular Pain |
| title | Pore dilation occurs in TRPA1 but not in TRPM8 channels |
| title_full | Pore dilation occurs in TRPA1 but not in TRPM8 channels |
| title_fullStr | Pore dilation occurs in TRPA1 but not in TRPM8 channels |
| title_full_unstemmed | Pore dilation occurs in TRPA1 but not in TRPM8 channels |
| title_short | Pore dilation occurs in TRPA1 but not in TRPM8 channels |
| title_sort | pore dilation occurs in trpa1 but not in trpm8 channels |
| url | http://www.molecularpain.com/content/5/1/3 |
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