The ion selectivity filter is not an activation gate in TRPV1-3 channels
Activation of TRPV1 channels in sensory neurons results in opening of a cation permeation pathway that triggers the sensation of pain. Opening of TRPV1 has been proposed to involve two gates that appear to prevent ion permeation in the absence of activators: the ion selectivity filter on the externa...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/51212 |
| _version_ | 1828384536678891520 |
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| author | Andrés Jara-Oseguera Katherine E Huffer Kenton J Swartz |
| author_facet | Andrés Jara-Oseguera Katherine E Huffer Kenton J Swartz |
| author_sort | Andrés Jara-Oseguera |
| collection | DOAJ |
| description | Activation of TRPV1 channels in sensory neurons results in opening of a cation permeation pathway that triggers the sensation of pain. Opening of TRPV1 has been proposed to involve two gates that appear to prevent ion permeation in the absence of activators: the ion selectivity filter on the external side of the pore and the S6 helices that line the cytosolic half of the pore. Here we measured the access of thiol-reactive ions across the selectivity filters in rodent TRPV1-3 channels. Although our results are consistent with structural evidence that the selectivity filters in these channels are dynamic, they demonstrate that cations can permeate the ion selectivity filters even when channels are closed. Our results suggest that the selectivity filters in TRPV1-3 channels do not function as activation gates but might contribute to coupling structural rearrangements in the external pore to those in the cytosolic S6 gate. |
| first_indexed | 2024-12-10T05:04:54Z |
| format | Article |
| id | doaj.art-4a11084e0a4e45eba32137fdb49b2619 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:04:54Z |
| publishDate | 2019-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4a11084e0a4e45eba32137fdb49b26192022-12-22T02:01:16ZengeLife Sciences Publications LtdeLife2050-084X2019-11-01810.7554/eLife.51212The ion selectivity filter is not an activation gate in TRPV1-3 channelsAndrés Jara-Oseguera0https://orcid.org/0000-0001-5921-9320Katherine E Huffer1Kenton J Swartz2https://orcid.org/0000-0003-3419-0765Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesActivation of TRPV1 channels in sensory neurons results in opening of a cation permeation pathway that triggers the sensation of pain. Opening of TRPV1 has been proposed to involve two gates that appear to prevent ion permeation in the absence of activators: the ion selectivity filter on the external side of the pore and the S6 helices that line the cytosolic half of the pore. Here we measured the access of thiol-reactive ions across the selectivity filters in rodent TRPV1-3 channels. Although our results are consistent with structural evidence that the selectivity filters in these channels are dynamic, they demonstrate that cations can permeate the ion selectivity filters even when channels are closed. Our results suggest that the selectivity filters in TRPV1-3 channels do not function as activation gates but might contribute to coupling structural rearrangements in the external pore to those in the cytosolic S6 gate.https://elifesciences.org/articles/51212TRP channelTRPV3ion channel gatingTRPV2activation gate |
| spellingShingle | Andrés Jara-Oseguera Katherine E Huffer Kenton J Swartz The ion selectivity filter is not an activation gate in TRPV1-3 channels eLife TRP channel TRPV3 ion channel gating TRPV2 activation gate |
| title | The ion selectivity filter is not an activation gate in TRPV1-3 channels |
| title_full | The ion selectivity filter is not an activation gate in TRPV1-3 channels |
| title_fullStr | The ion selectivity filter is not an activation gate in TRPV1-3 channels |
| title_full_unstemmed | The ion selectivity filter is not an activation gate in TRPV1-3 channels |
| title_short | The ion selectivity filter is not an activation gate in TRPV1-3 channels |
| title_sort | ion selectivity filter is not an activation gate in trpv1 3 channels |
| topic | TRP channel TRPV3 ion channel gating TRPV2 activation gate |
| url | https://elifesciences.org/articles/51212 |
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