Ion channel regulation and function

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.

Properties of rhythmogenic currents in spinal Shox2 interneurons across postnatal development

The paper investigates how rhythmogenic ionic currents and ion channel expression in spinal Shox2 interneurons change during postnatal development in mice.

Structure-based mechanism of RyR channel operation by calcium and magnesium ions

The paper elucidates the structural mechanism of RyR channel operation by Ca2+ and Mg2+ ions using bioinformatics and statistical modeling.

Disruption of a side portal pathway permits closed-state inactivation by BK β subunit N-termini

The paper investigates how mutations in BK channel β subunit residues affect inactivation by altering access to the central cavity through the side portal pathway.

A rich conformational palette underlies human CaV2.1-channel availability

This study investigates the structural dynamics of CaV2.1 voltage-sensor domains and their role in voltage-dependent inactivation and synaptic function.

The pentameric chloride channel BEST1 is activated by extracellular GABA

This study shows that BEST1, a chloride channel, is directly activated by extracellular GABA, with structural and functional evidence revealing the mechanism of GABA-induced channel opening.

Regulation of input excitability in human and mouse parvalbumin interneurons by Kir potassium channels

This study shows that Kir potassium channels regulate input excitability in parvalbumin interneurons similarly in human and mouse, inhibiting them during postsynaptic potentials.

Turning a Kv channel into hot and cold receptor by perturbing its electromechanical coupling.

This study shows that a single mutation can drastically alter the temperature response of Kv channels by modifying their electromechanical coupling.

Functionally-Coupled Ion Channels Begin Co-assembling at the Start of Their Synthesis

The paper shows BK and CaV1.3 channels begin assembling into hetero-clusters intracellularly before reaching the plasma membrane.

The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway

This study shows tofogliflozin induces vasodilation in rabbit arteries by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway, independent of endothelium or PKA.

NALCN/Cch1 channelosome subunits originated in early eukaryotes and are fully conserved in animals, fungi, and apusomonads

This study identifies the ancient eukaryotic origins and conservation of NALCN/Cch1 channelosome subunits across animals, fungi, and apusomonads.

SLO2.1/NALCN Functional Complex Activity in Mouse Myometrial Smooth Muscle Cells During Pregnancy.

This study investigates the role of the SLO2.1/NALCN complex in regulating mouse myometrial smooth muscle cell membrane potential across pregnancy, finding its activity decreases as pregnancy progresses.

Domain Coupling in Allosteric Regulation of SthK Measured Using Time-Resolved Transition Metal Ion FRET

This study uses time-resolved tmFRET to analyze conformational changes and energetics in the CNBD of SthK, showing that transmembrane domains make the activating conformation more favorable.

Cotranslational membrane insertion of the voltage-sensitive K+ channel KvAP

The paper investigates the cotranslational membrane insertion of the KvAP voltage-sensitive ion channel using Force Profile Analysis, revealing three distinct insertion steps and the role of charged residues and helical structures.

Photoperiodic Regulation of SK Channels in Dorsal Raphe Serotonin Neurons

This study shows that photoperiod modulates SK channel function in dorsal raphe serotonin neurons through post-transcriptional mechanisms, linking seasonal cues to mood-related behaviors.

Molecular dynamics of membrane partitioning of nifedipine prior to binding calcium channel Cav1.1

This study uses MD simulations to analyze the membrane partitioning of nifedipine before its binding to Cav1.1, showing drug-membrane interactions occur faster than overall binding.

AI-Based Discovery and CryoEM Structural Elucidation of a KATP Channel Pharmacochaperone

The paper identifies a novel KATP channel pharmacochaperone, Aekatperone, using AI screening and cryoEM, showing reversible inhibition and functional recovery of trafficking mutants.

Differential contributions of CaV2.2, GIRK, and HCN channels to the modulation of excitability by alpha-conotoxin Vc1.1 and baclofen effects in somatic and visceral sensory neurons

This study investigates how CaV2.2, GIRK, and HCN channels modulate excitability in somatic and visceral sensory neurons in response to Vc1.1 and baclofen, finding distinct mechanisms in different neuron types.

Ion Channel Reaction Networks: Dielectric Screening and the Importance of Off-Pathway Flux

This paper uses multiscale responsive kinetic modeling to study ion channel mechanisms, showing that off-pathway flux and dielectric screening significantly influence current profiles and channel behavior.

The sodium leak channel NALCN is regulated by neuronal SNARE complex proteins

The paper shows that SNARE complex proteins inhibit NALCN channel activity and that reducing NALCN currents promotes cell survival in syntaxin-depleted cells.

Inwardly rectifying potassium channels regulate membrane potential polarization and direction sensing during neutrophil chemotaxis

This study identifies Kir7.1's role in maintaining membrane potential and directional sensing during neutrophil chemotaxis, showing its necessity for polarized depolarization and chemotactic movement.

Ctenophores and parahoxozoans independently evolved complex and functionally diverse sets of voltage-gated K+ channels

The paper identifies and functionally characterizes voltage-gated K+ channels in ctenophores, showing independent evolution of diverse subtypes similar to those in cnidarians and bilaterians.

Structure and dynamics of a multidomain ligand-gated ion channel revealed under acidic conditions

The paper uses cryo-EM, molecular dynamics, and small-angle neutron scattering to characterize an open and closed state of the bacterial ion channel DeCLIC under acidic conditions, revealing structural and dynamic mechanisms of gating.

CryoEM Structure of the human THIK-1 K2P K+ Channel Reveals a Lower 'Y-gate' Regulated by Lipids and Anaesthetics

The paper presents a cryoEM structure of the human THIK-1 K2P K+ channel, revealing structural features and regulatory mechanisms involving lipids and anaesthetics.

Structure of the human K2P13.1(THIK-1) channel reveals a novel hydrophilic pore restriction and lipid cofactor site

This paper presents cryo-EM structures of human K2P13.1 (THIK-1) revealing a novel hydrophilic pore restriction and lipid cofactor site, with implications for modulator development.

A conserved mechanism of LRRC8 channel inhibition by distinct drugs

This study investigates how zafirlukast and pranlukast inhibit LRRC8 channels by identifying their binding sites and showing they destabilize the channel pore.

Orthosteric interactions with PIP2 activate TMEM16A channels

This study identifies how PIP2 interacts with TMEM16A channels to activate them, revealing structural and functional insights for drug development.

Activity and function of the endothelial sodium channel is regulated by the effector domain of MARCKS like protein 1 in mouse aortic endothelial cells

This study shows that MLP1's effector domain and PIP2 regulate EnNaC activity in mouse aortic endothelial cells by affecting membrane association and fluidity.

Key residue Unlocks Dual PIP2-Dependent and Independent Gating in G Protein-Gated Inwardly Rectifying Potassium Channels

The paper identifies R92 as a key residue in GIRK2 channels that modulates both PIP2-dependent and independent gating mechanisms through experimental and structural analyses.

Specific presynaptic functions require distinct Drosophila Cav2 splice isoforms

This study shows that alternative splicing of the Drosophila Cav2 gene regulates distinct presynaptic functions, with different splice variants affecting synaptic vesicle release and short-term plasticity.