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The ion selectivity filter is not an activation gate in TRPV1-3 channels
Andrés Jara-Oseguera1, Katherine E Huffer1, Kenton J Swartz1
1Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.
Elife
|November 15, 2019
Summary
The ion selectivity filter in TRPV1-3 channels allows cation permeation even when closed, suggesting it doesn't act as an activation gate. This filter may couple external pore changes to the internal S6 gate.
Area of Science:
- Molecular biology
- Neuroscience
- Ion channel function
Background:
- Transient Receptor Potential Vanilloid 1 (TRPV1) channels in sensory neurons mediate pain sensation.
- TRPV1 channel activation involves opening a cation permeation pathway, proposed to be regulated by two gates: the external selectivity filter and the internal S6 helices.
Purpose of the Study:
- To investigate the role of the ion selectivity filter in TRPV1-3 channels as an activation gate.
- To determine if cations can permeate the selectivity filter of closed TRPV1-3 channels.
Main Methods:
- Measurement of thiol-reactive ion access across the selectivity filters of rodent TRPV1-3 channels.
- Utilizing structural evidence and functional assays to probe channel gating mechanisms.
Main Results:
- Results indicate that the ion selectivity filters in TRPV1-3 channels are dynamic structures.
- Cations were demonstrated to permeate the selectivity filters even in the absence of channel activators (i.e., when channels are closed.
Conclusions:
- The ion selectivity filters of TRPV1-3 channels do not function as activation gates.
- These filters may play a role in signal transduction, coupling conformational changes in the external pore to the internal S6 gate.
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