Ion channel regulation and function

State-specific binding thermodynamics predicts ligand efficacy across ion-channel families.

The paper uses free energy perturbation to predict ligand efficacy in ion channels by analyzing state-specific binding thermodynamics across multiple families.

The nanoscopic submyelin space mediates efficient K+ uptake and shapes nodal action potentials

The paper develops a finite element model to study K+ dynamics and action potential behavior at the node of Ranvier, revealing how periaxonal K+ buffering enables high-frequency conduction.

Spatial organization of voltage-gated ion channel expression across molecularly defined neuronal populations in the mouse mammillary bodies

The paper maps the spatial distribution of voltage-gated ion channels in mouse mammillary bodies using FISH and links it to molecularly defined neuronal populations.

Phosphorylation of the Kv7.4 B helix reorganizes calmodulin interactions and reduces PIP2 binding

This study shows phosphorylation of Thr552 in Kv7.4 reduces PIP2 binding and channel activity while reorganizing calmodulin interactions.

Gβγ dually regulates the M current via increased channel surface expression and PIP2 sensitivity

This study shows Gβγ enhances M-current by increasing channel surface expression and stabilizing PIP2 coupling in Xenopus laevis oocytes.

Cinnamaldehyde interacts with the local anesthetic pocket of the NaV 1.5 channel

This study shows that cinnamaldehyde blocks NaV1.5 channels in a voltage-dependent manner, similar to local anesthetics, and identifies key residues involved in this interaction.

Structural conservation of the gabapentinoid binding site in human and Caenorhabditis elegans α2δ subunits: a docking and molecular dynamics perspective

This study compares the structural features of human and C. elegans alpha2delta subunits to assess gabapentinoid binding site conservation using docking and molecular dynamics simulations.

Asymmetric turnover dynamics of Nav1.6 voltage-gated sodium channels at the axon initial segment

The paper uses a genetically engineered mouse to study Nav1.6 sodium channel turnover dynamics at the axon initial segment, revealing spatially asymmetric turnover and its role in AIS quality control.

Mechanistical and structural basis of Kv channel inhibition by 4 aminopyridine

This study determines the structure of Kv channels bound to 4AP, showing it binds the closed state and enters via membrane-facing fenestrations, explaining its inhibitory mechanism.

A New Disease Gene for Hypokalemic Periodic Paralysis, KCNA7, Established in a Multigenerational Family

The paper identifies a KCNA7 missense variant as a new disease gene for hypokalemic periodic paralysis through genetic, structural, and electrophysiological analyses in a multigenerational family.

Basolateral localization of Kcnj15 in branchial ionocytes of the seawater pufferfish Takifugu rubripes

The paper identifies the basolateral localization of Kcnj15 in gill ionocytes of the seawater pufferfish and shows its expression stability under hypoosmotic conditions.

Identification of sodium/myo-inositol transporter 1 as a major determinant of arterial contractility

This study shows that altering SMIT1 membrane abundance significantly affects arterial contractility by modulating Kv7 channel and Gβγ subunit interactions.

The length constant, time constant and velocity of a propagating action potential

The paper defines new length and time constants for action potential propagation and shows their relationship to propagation velocity.

PRRT2 as an auxiliary regulator of Nav channel slow inactivation

This study identifies PRRT2 as a regulator of Nav channel slow inactivation, showing its role in maintaining cortical resilience to hyperexcitability.

Calmodulin controls spatial and temporal specificity of calcium-induced calcium release

This study shows that calmodulin regulates calcium dynamics in neurons by modulating RyR2 and PMCA, with implications for aging and Alzheimer's disease.

The MscS channel from Corynebacterium glutamicum uses a non-canonical gating mechanism

This study shows that CgMscS from Corynebacterium glutamicum opens at higher membrane tension than EcMscS and uses a distinct gating mechanism not based on the 'lipids-move-first' model.

The wild-type hERG cryo-EM structure fails to support conduction and evolve toward an inactivated-like selectivity filter conformation in molecular dynamics simulations

The study uses molecular dynamics simulations to show that wild-type hERG fails to conduct K+ and evolves toward an inactivated-like conformation, contrasting with the N629D mutant which maintains conductivity.

Current-voltage characteristics of K+ channels estimated by MD simulations and Markov State Models

The paper estimates current-voltage characteristics of K+ channels using Markov State Models from MD simulations, showing agreement with direct simulations at low potentials.

Mechanosensitive channels dominate the minimal ion channelrepertoire in prokaryotes

The paper identifies five ion channel architectures essential for prokaryotic viability, with mechanosensitive channels being the most abundant.

Structural identification of the RY12 domain of RyR1 as an ADP sensor and the target of the malignant hyperthermia therapeutic dantrolene

This study identifies the RY12 domain of RyR1 as an ADP sensor and reveals dantrolene's binding mechanism through cryo-EM structures.

PIP2 Binding at Allosteric Site Blocks Activation in Human Rod CNG Channels

This study identifies how PIP2 binding at an allosteric site inhibits human rod CNG channels by stabilizing non-conductive conformations.

Scorpion toxin peptide BMK86-P1 achieves mutation-reversible inhibition of KCNA2 at the cost of reduced efficacy in heteromers and murine neurons

The paper demonstrates that the scorpion toxin BMK86-P1 selectively inhibits KV1.2 homomers but not heteromers, with a mutation reducing its efficacy and altering channel activation.

Mechanism of Gating and Isoform-Specific Inhibition in Renal CLC Chloride Channels

The paper investigates how BIM1 selectively inhibits CLC-Ka over CLC-Kb by analyzing cryo-EM structures and showing that interactions with a conserved lysine and dynamic gating-loop behavior underlie this selectivity.

Structural basis for nutrient-activated channel opening in bacterial spore germination receptors

The paper reports cryo-EM structures of GerA, revealing how nutrient binding triggers channel opening through allosteric switches and subunit interactions.

Characterization of an early-diverging KCNE potassium-channel auxiliary subunit in the jawless vertebrate lamprey

This study functionally characterizes a KCNE-like gene in lamprey, showing species-specific compatibility with KCNQ1 and an inhibitory effect similar to KCNE4.

State-dependent binding of the wedge domain controls inactivation of the mechanosensitive ion channel PIEZO1

This study investigates how the wedge domain of PIEZO1 contributes to its inactivation through structural and functional analyses.

Protein semi-synthesis enables real-time optical tracking of intracellular conformational changes during sodium channel inactivation

This study uses protein semi-synthesis and voltage-clamp fluorometry to track real-time conformational changes in the cardiac sodium channel NaV1.5 during inactivation.

K2P Channels Regulate Presynaptic Organisation through a Membrane Potential-Independent Mechanism

This study identifies a membrane potential-independent role for the K2P channel TWK-40 in regulating presynaptic organisation through intracellular potassium levels and interactions with PYK-1 and transcription factors.

Biophysical Characterization of the human Nav1.9 sodium channel in trigeminal ganglia and dorsal root ganglia neurons

This study characterizes Nav1.9 channel biophysical properties in human trigeminal and dorsal root ganglia neurons, revealing distinct kinetic and voltage-dependent differences.

Temperature and frequency dependence of conduction along sympathetic preganglionic axons

The paper examines how temperature and activity affect conduction reliability in sympathetic preganglionic axons, finding that slower-conducting axons are more vulnerable and show frequency-dependent changes.