Ion channel regulation and function

One model to rule them all: unification of voltage-gated potassium channel models via deep non-linear mixed effects modelling

The paper develops a unified deep non-linear mixed effects model for voltage-gated potassium channels, improving fit over existing models and enabling modeling of diverse channel types.

Large-Scale Structure-Based Virtual Screening Identifies Diverse KNa1.1 (KCNT1) Potassium Channel Inhibitors

This study identifies eight structurally diverse KCNT1 channel inhibitors through virtual screening and experimental validation, offering potential new treatments for KCNT1-associated epilepsy.

Integrating AI and molecular modeling for structural prediction of a closed state of the hERG channel

This study uses AI-based structural modeling to predict and compare closed-state conformations of the hERG channel, revealing insights into its dynamics and potential drug interactions.

Presynaptic CaV2.1 calcium dependent facilitation is essential for faithful auditory information transfer

The paper investigates the role of CaV2.1 calcium-dependent facilitation in auditory synaptic transmission, finding that its absence reduces synaptic reliability and precision.

Kv1.3 palmitoylation regulates spatial distribution and channel removal from the immunological synapse

This study shows that Kv1.3 palmitoylation regulates its spatial distribution and removal from the immunological synapse, impacting T cell activation and autoimmune disease.

Atomic structure and dynamics of the mechanosensitive channel MscL from E. coli by cryo-EM and solid-state NMR

This study uses cryo-EM and solid-state NMR to determine the structure and dynamics of MscL from E. coli, revealing lipid-protein interactions that drive mechanosensitive gating.

Structural Insights into the Integration of Temperature and pH by Sperm Calcium Channel CatSper

This study identifies how CatSper channels integrate temperature and pH signals through structural and evolutionary analyses in sperm.

Proton tunneling at the ryanodine receptor Ca2+ activation site provides temperature-invariant noise for robust Ca2+-induced Ca2+ release

Allosteric Mechanisms Underlying Long QT Syndrome Type 2 (LQT2) Associated Mutations in hERG Channels

This study uses molecular dynamics simulations to show that LQT2 mutations disrupt the selectivity filter structure, impairing channel trafficking, and that some variants can correct these defects.

LRRC55 modulates BK channels to support Purkinje cell plasticity and motor coordination

This study identifies LRRC55 as an auxiliary subunit of BK channels in Purkinje cells, showing its role in motor coordination and synaptic plasticity through BK channel modulation.

MscM uses a novel gating mechanism for bacterial mechanosensitive channels

This study characterizes the structure and function of MscM, revealing that its cytoplasmic domain mediates channel gating through conformational changes, differing from other MscS-like channels.

SK2/3 CHANNELS COUPLE WITH T-TYPE CA2+ CHANNELS TO GATE SPINAL LOCOMOTOR RHYTHM GENERATION

The paper identifies SK2/3 channels coupled with T-type Ca2+ channels as a mechanism gating spinal locomotor rhythm generation, showing their role in initiating and terminating locomotor activity.

Comprehensive classification of HCN1 variants linked to neurodevelopmental disorders with and without epilepsy

This study functionally classifies HCN1 variants in patients with neurodevelopmental disorders, finding genotype-phenotype correlations and potential therapeutic targets.

A scaffold attachment factor PHM-2 regulates synaptic transmission through SLO-2 potassium channel in C. elegans

This study identifies PHM-2 as a regulator of synaptic transmission in C. elegans by modulating SLO-2 potassium channel activity through posttranscriptional control.

Parallel analysis of voltage-gated sodium channel subunits reveals preferential colocalizations of beta-1/Nav1.1 and beta-2/Nav1.2

The paper examines the co-expression patterns of voltage-gated sodium channel subunits in neurons across different brain regions and developmental stages, revealing distinct subunit combinations in inhibitory and excitatory neurons.

Developmental mechanisms contributing to non-linear firing dynamics in spinal motoneurons of the postnatal mouse

This study investigates how ion channels contribute to non-linear firing dynamics in postnatal mouse spinal motoneurons, showing that PICs and other channels like KCNQ, Kv1.2, and HCN play key roles in sustaining firing.

Structure of a pH-sensitive pentameric ligand-gated ion channel from the Sarcoptes scabies mite

This study determines the structure of a pH-sensitive ion channel from the scabies mite and shows how ivermectin modulates its activity through pH-dependent conformational changes.

A KCNC1 Variant Linked to Rett Syndrome Disrupts ER to Golgi Trafficking of Kv3.1 Channel

This study identifies a KCNC1 variant linked to Rett syndrome that disrupts ER to Golgi trafficking of Kv3.1 channels, affecting neuronal excitability.

Discovery of the first small-molecule extracellular inhibitor of KCa3.1

This paper discovers a small-molecule inhibitor of KCa3.1 channels by combining molecular dynamics simulations and high-throughput screening.

Predicting Binding Affinities for the Binding Domain of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Isoforms Using Free-Energy Perturbation

The paper uses free-energy perturbation to calculate binding affinities of cAMP to HCN isoforms 1-4 CNBDs, revealing differences in channel activation sensitivity.

Pro-tumoral Ca2+ signaling is dependent on Ca-alpha1T and Slowpoke channels in Drosophila melanogaster glioma

This study identifies Ca-alpha1T and Slowpoke channels as essential for pro-tumorigenic Ca2+ signaling in Drosophila gliomas, with Slowpoke showing therapeutic potential.

Temperature and pH-dependent Potassium Currents of Muscles of the Stomatogastric Nervous System of the Crab, Cancer borealis

This paper shows that stomach muscles of Cancer borealis hyperpolarize with warming and operate optimally within a narrow pH window, mediated by K2P channels that reduce excitability and maintain neuromuscular function under environmental change.

Molecular assembly of the KCNQ1-KCNE1-BACE1 complex

This study investigates the molecular interactions between KCNQ1, KCNE1, and BACE1 using multiple assays, revealing domain-specific contributions and functional additivity.

Persistent Adaptation through Dual-Timescale Regulation of Ion Channel Properties

The paper demonstrates how neurons use dual-timescale regulation of ion channel properties to achieve persistent adaptation to environmental perturbations.

Coupling Between Functionality and Trafficking to the Axon Initial Segment in KCNQ2/3 K+ Channels

This study investigates how functionality and trafficking of KCNQ2/3 K+ channels are coupled, showing that low-activity mutations disrupt AIS targeting via ankyrin-G interaction.

Non-syndromic autism-associated SCN2A variants selectively exert dominant-negative effects on NaV1.2 channels.

The paper investigates the functional impact of SCN2A variants associated with non-syndromic autism, finding that only non-syndromic ASD variants cause dominant-negative effects on Nav1.2 channels.

Sequential membrane remodeling by cholesterol distinctly modulates HCN channels in naïve and neuropathic DRG neurons

This study investigates how cholesterol modulates HCN channels in DRG neurons through sequential membrane remodeling, showing distinct effects in naive and neuropathic conditions.

Asymmetry-induced distinct mechanisms and the transporting role of sodium in bacterial fluoride channel Fluc

This study uses molecular dynamics simulations to reveal distinct transport mechanisms in Fluc's dual-pore structure and identifies a sodium ion's role as a dynamic cofactor in fluoride transport.

Tuning the gate and the gear: The LRRC26 (γ1) subunit modulates intrinsic gating and voltage-sensor coupling of the BK channel

This study shows that the γ1 subunit of BK channels increases the equilibrium constant for channel opening by destabilizing the closed state and enhancing voltage-sensor-pore coupling.

The TWK-26/KCNK3 potassium channel and FLR-4 protein kinase coordinate nutrient absorption in the C. elegans intestine

This study shows that the TWK-26/KCNK3 potassium channel and FLR-4 protein kinase work together in C. elegans to regulate nutrient absorption and metabolic homeostasis.