Ion channel regulation and function

Mechanisms of KCNQ1 gating modulation by KCNE1/3 for cell-specific function

This study investigates how KCNE1 and KCNE3 modulate KCNQ1 gating through PIP2-dependent mechanisms, revealing distinct roles in voltage sensitivity and GPCR regulation across cell types.

Voltage-sensor trapping of cardiac Na+ channels by Mg-protoporphyrin impairs cancer cell migration

This study identifies MgPpIX as a potent and specific inhibitor of hNaV1.5, which suppresses cancer cell migration.

An Allosteric Model for Electromechanical Coupling in Cardiac CNBD Channels

The paper proposes an allosteric model for electromechanical coupling in cardiac CNBD channels, explaining biphasic activation behaviors through voltage-sensor transitions and conformational coupling modes.

The bile acid-sensitive ion channel is gated by Ca2+-dependent conformational changes in the transmembrane domain

This study determines the structure of human BASIC with and without Ca2+ using cryo-EM and shows Ca2+-dependent conformational changes in the transmembrane domain and β-linkers, revealing how Ca2+ modulates ion flow through the channel.

Differential roles of NaV1.2 and NaV1.6 in neocortical pyramidal cell excitability

This study investigates the distinct roles of NaV1.2 and NaV1.6 in neocortical pyramidal cell excitability using inhibitors and genetic modifications to selectively block each isoform.

Optical single-channel recording via diffusional confinement in membrane tethers

The paper demonstrates a method to enhance single-channel transport detection by confining substrate diffusion in membrane tethers, enabling observation of individual Ca2+ transport events.

The evolutionary path of the epithelial sodium channel delta-subunit in Cetartiodactyla points to a role in sodium sensing

The paper traces the evolutionary changes in the ENaC delta-subunit in cetartiodactyls, suggesting it functions in sodium sensing and became obsolete in marine cetaceans.

CACNA1C TS-II variants alter single-cell dynamics in computational models of cortical pyramidal cells

The paper investigates how CACNA1C variants affect single-cell dynamics in computational models of cortical pyramidal cells, identifying altered calcium regulation and dendritic retraction in Timothy Syndrome type II.

A privileged ER compartment for post-translational heteromeric assembly of an ion channel

The paper identifies a specialized ER compartment that sequesters hERG1b subunits, enabling post-translational heteromeric assembly with hERG1a instead of degradation.

Investigate Channel Rectifications and Neural Dynamics by An Electrodiffusive Gauss-Nernst-Planck Approach

This study introduces a Gauss-Nernst-Planck approach to analyze how electrodiffusive dynamics influence ion channel rectification and neural activity, revealing new insights into membrane conductivity and neural firing mechanisms.

Cell Settling, Migration, and Stochastic Cancer Expression Suggest Potassium Flux Per H+- Sensitive KCN Members Associated with Oncogenes and Histone/DNA Modulators Potentially Initiates pH-Reversal

The paper investigates potassium flux through H+-sensitive KCN channels in cancer cells, linking it to pH reversal and oncogenic processes through differential gene expression analysis.

The molecular basis of sodium-dependent fluoride export by the eukaryotic fluoride channel FEX

This study identifies the molecular mechanism of sodium-dependent fluoride export by FEX proteins using electrophysiology, cryo-EM, and simulations.

Prokaryotic mechanosensitive channels mediate copper influx

The paper shows that mechanosensitive channels in prokaryotes, like E. coli, mediate copper influx, challenging the idea that cytoplasmic copper uptake is unnecessary in these organisms.

Structural Basis for Voltage Gating and Dalfampridine Binding in the Shaker Potassium Channel Revealed by Closed-State Model

The paper presents a structural model of the closed Shaker potassium channel, revealing how voltage sensor movement drives pore opening and identifies a binding site for dalfampridine.

Neurogranin Unlocks the L-type Ca2+ Channel and Directs Calmodulin Delivery

This study shows neurogranin binds to the L-type Ca2+ channel, facilitates calmodulin delivery, and enhances channel function through dynamic interactions.

A lipid plug affects K2P6.1(TWIK-2) function

This paper identifies a lipid plug in K2P6.1 channels that regulates their activity by occupying the central cavity and preventing ion permeation.

Asymmetric nature of MscL opening revealed by molecular dynamics simulations

This paper uses molecular dynamics simulations to study the asymmetric opening of MscL mutants under tension, revealing the S1 state and its free energy profile.

The Pseudomonas aeruginosa Tse4 toxin assembles ion-selective and voltage-sensitive ion channels to couple membrane depolarisation with K+ efflux

This study identifies Tse4 as a pore-forming toxin that forms ion-selective channels, linking membrane depolarisation to K+ efflux in competing bacteria.

Kv2/Kv6.4 heteromeric potassium channels are expressed in spinal motor neurons and localized at C-bouton synapses

The paper identifies a specific Kv2/Kv6.4 channel subtype in spinal motor neurons localized at C-bouton synapses, showing dependence on Kv2 subunits for expression and clustering.

Mechanism of Lipid-Dependent Thermosensation in an Ion Channel

This study identifies a salt bridge in the bacterial ion channel SthK that functions as a temperature sensor, with lipid composition modulating its sensitivity to temperature changes.

Parkinson's Disease-Linked Kir4.2 Mutation R28C Leads to Loss of Ion Channel Function

This study investigates the impact of the Kir4.2R28C mutation on channel function and cellular processes, finding it causes loss of function and disrupts protein stability and trafficking.

CLUSTERING DYNAMICALLY MODULATE THE BIOPHYSICS OF VOLTAGE-GATED SODIUM CHANNELS: HOW NANOSCALE PHENOMENA DETERMINE HEALTH AND DISEASE

The paper shows that clustering of voltage-gated sodium channels affects their biophysics, leading to different pharmacological responses and potential therapeutic implications.

Deciphering Ca2+ Permeation and Valence Selectivity in Cav1: Molecular Dynamics Simulations Reveal the Three-Ion Knock-on Mechanism

This study uses molecular dynamics simulations to reveal the three-ion knock-on mechanism governing calcium ion permeation and valence selectivity in CaV1 channels.

IQM-22110 as a selective KV4.3/KChIP3 modulator. Molecular determinants of the KChIP3 binding site

This study identifies IQM-22110 as a selective KV4.3/KChIP3 modulator, showing it binds specifically to KV4.3/KChIP3 and not KV4.3/KChIP2 or KV4.3 alone.

Disease-associated Kv1.3 variants are energy compromised with impaired nascent chain folding.

This study investigates how disease-associated Kv1.3 variants affect protein folding and stability, finding that R114G variant shows reduced folding probability and structural instability.

Effective Polarization in Potassium Channel Simulations: Ion Conductance, Occupancy, Voltage Response, and Selectivity

This paper improves molecular dynamics simulations of potassium channels by incorporating polarization effects, achieving accurate predictions of conductance, ion occupancy, voltage response, and selectivity.

Thermosensitivity of TREK K2P channels is controlled by a PKA switch and depends on the microtubular network

This study identifies the C-terminal domain as the temperature sensor in TREK channels and shows that microtubule interaction and PKA phosphorylation regulate their thermosensitivity.

Electric field-induced pore constriction in the human Kv2.1 channel

The paper uses cryo-EM to show that hyperpolarization-induced displacement of the S4 helix in Kv2.1 channels causes pore constriction by altering interactions with S6 helices, similar to EAG1 channels.

Painless Nav1.7 mutations reveal function-critical residuesin the outer vestibule and N-terminus

The paper functionally characterizes six SCN9A missense variants associated with CIP, revealing that they cause complete loss-of-function through structural changes in the extracellular vestibule, ion selectivity filter, and N-terminus.

Structure of the human TWIK-2 potassium channel and its inhibition by pimozide

This paper reports the cryo-EM structure of the human TWIK-2 potassium channel and shows that pimozide inhibits it by displacing acyl chains and blocking ion conduction.