Sep 2026· Proceedings of the National Academy of Sciences of the United States of America· Vol 123· 0 citations· 76 references
Medicine
TL;DR
This work identifies a conserved gating crosstalk mechanism linking the activation gate to the width of the selectivity filter entrance, which regulates ion permeation rate by tuning ion occupancy at the selectivity filter.
Abstract
Significance Potassium channels regulate electrical signaling by transporting K+ across cell membranes. This activity is controlled by multiple gates, yet how these gates interact remains not entirely understood. We identify a conserved gating crosstalk mechanism linking the activation gate to the width of the selectivity filter entrance, which regulates ion permeation rate by tuning ion occupancy at the selectivity filter. This model illustrates the functional implications of the state-dependent differences in filter entrance size revealed by experimental structures from the Protein Data Bank. Our work thus constructs a direct link between simulations and experiments and provides a comprehensive view of how multiple gates cooperate to control potassium channel function.
Neuronal ion channels have well-established effects on synaptic plasticity, in many cases by influencing pathways that depend on membrane excitability. Here we find that a C. elegans two-pore domain potassium (K2P) channel, TWK-40, regulates presynaptic organisation through a membrane potential-independent mechanism. I...
Jun Meng, Neeraja Ramakrishnan, Yi Li et al.· bioRxiv· 0 citations
Significance Developing drugs that selectively target closely related ion channel isoforms remains a major challenge because these proteins often share highly conserved drug-binding sites. Here, we show that selective activation of Kv7 potassium channel isoforms by the rosemary-derived metabolite carnosic acid (CA) ari...
Rían W. Manville, Lorenzo Foglia, Ryan F. Yoshimura et al.· Proceedings of the National...· 0 citations
Voltage-gated sodium (NaV) channels are critical transmembrane proteins responsible for the initiation and propagation of electrical signals in excitable tissues. They consist of a large α subunit and auxiliary β subunits. Together, the voltage sensing, ion selectivity, and rapid gating transitions regulate neuronal, m...
João Pedro Boazinha, João Carneiro, Nuno M. F. S. A. Cerqueira et al.· Pharmacological Research· 0 citations
Ion channels possess selectivity filters that are hardwired to ensure the selective passage of ions. Lysosomal two-pore channels are unusual as they are able to switch their cation selectivity in an agonist-specific manner, allowing differential control of organellar activity. TPC2 is permeable to Ca2+ when activated b...
Using molecular dynamics, computational electrophysiology, and single-channel recordings, Arcario et al. identify a cryptic extracellular lateral fenestration in the pentameric ligand-gated ion channel, ELIC, that becomes the dominant cation conduction pathway. Expansion of this pathway is required to reproduce experim...
Mark J. Arcario, Elizabeth J. Wu-Chen, Yuna Shim et al.· The Journal of General Physi...· 0 citations
Abstract Escherichia coli has a single K+ channel gene, kch, that produces a K+ channel with six transmembrane segments and a cytosolic Regulate Conductance of K+ channels (RCK) domain. RCK domains are present in both eukaryotic and prokaryotic organisms and known to regulate ion channel activity upon binding of an ion...
Brian Morote-Costas, Ya-Ping Pan, Lie Wang et al.· PNAS Nexus· 0 citations
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