The ion selectivity filter is not an activation gate in TRPV1-3 channels
Abstract
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 and compounds 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.
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All data generated or analysed during this study are shown in the manuscript and supporting files. The corresponding authors can be contacted if the raw data is required by anyone.
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Funding
National Institute of Neurological Disorders and Stroke (K99 Pathway to Independence Award)
- Andrés Jara-Oseguera
National Institute of Neurological Disorders and Stroke (Intramural Research Program NS002945)
- Kenton J Swartz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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