ArticleBiophysical journal2018
Mechanism of Mechanosensitive Gating of the TREK-2 Potassium Channel.
Article in Biophysical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- One pocket to activate them all (?): Efforts on understanding the modulator pocket in K2P channels.Channels (Austin, Tex.) · 2026Review
- Gating crosstalk in potassium channels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Models of Cellular Mechanosensation.Results and problems in cell differentiation · 2026Review
- Atomistic mechanism of noncanonical voltage gating in KScience advances · 2025Article
- Effective polarization in potassium channel simulations: Ion conductance, occupancy, voltage response, and selectivity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease.Structure (London, England : 1993) · 2025Article
- Do selectivity filter carbonyls in KJournal of structural biology: X · 2024Article
- Constitutive sodium permeability in aProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Effect of two activators on the gating of a KBiophysical journal · 2024Article
- Article
- Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels.Nature communications · 2024Article
- Research progress of two-pore potassium channel in myocardial ischemia-reperfusion injury.Frontiers in physiology · 2024Review
- Interactions between selectivity filter and pore helix control filter gating in the MthK channel.The Journal of general physiology · 2023Article
- TREK channels in Mechanotransduction: a Focus on the Cardiovascular System.Frontiers in cardiovascular medicine · 2023Review
- Transition between conformational states of the TREK-1 K2P channel promoted by interaction with PIPBiophysical journal · 2022Article
- Allosteric coupling between transmembrane segment 4 and the selectivity filter of TALK1 potassium channels regulates their gating by extracellular pH.The Journal of biological chemistry · 2022Article
- 'C-type' closed state and gating mechanisms of K2P channels revealed by conformational changes of the TREK-1 channel.Journal of molecular cell biology · 2022Article
- Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium.Biology · 2021Article
- Molecular dynamics: a powerful tool for studying the medicinal chemistry of ion channel modulators.RSC medicinal chemistry · 2021Review
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2 authors.
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Abstract
The mechanism of mechanosensitive gating of ion channels underlies many physiological processes, including the sensations of touch, hearing, and pain perception. TREK-2 is the best-studied mechanosensitive member of the two-pore domain potassium channel family. Apart from pressure sensing, it responds to a diverse range of stimuli. Two states, termed "up" and "down," are known from x-ray structural crystallographic studies and have been suggested to differ in conductance. However, the structural details of the gating behavior are largely unknown. In this work, we used molecular dynamics simulations to study the conductance of the states as well as the effect of mechanical membrane stretch on the channel. We find that the down state is less conductive than the up state. The introduction of membrane stretch in the simulations shifts the state of the channel toward an up configuration, independent of the starting configuration, and also increases its conductance. The correlation of the selectivity filter state and the conductance supports a model in which the selectivity filter gates by a carbonyl flip. This gate is stabilized by the pore helices. We suggest a modulation of these helices by an interface to the transmembrane helices. Membrane pressure changes the conformation of the transmembrane helices directly and consequently also influences the channel conductance.
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