Ion channel regulation and function

The paper determines the structures of three ENaC complexes, revealing how subunit composition affects channel function through structural rearrangements.

This study identifies Slc7a5 and LMAN2 as regulators of Kv1.2 channel gating, showing they compete for interaction with the voltage sensor, leading to complex voltage-dependent behavior.

The paper identifies a brachiopod DEG/ENaC/ASIC channel activated by diarylamidines, distinct from other known ligand-gated channels.

This study shows cannabinoids inhibit mechanosensitive K2P channels, including disease-causing mutants, and reveals the mechanism of channel block via CBD binding.

This study presents cryo-EM structures of human NCX1 with PIP2 and SEA0400, revealing how these molecules modulate NCX1 activity through conformational changes.

This study presents cryoEM structures of TASK-1 and TASK-3 channels, revealing structural insights into their gating mechanism and pH sensitivity, and how mutations disrupt function in disease.

This study identifies two tiers of PKA substrate sites in CaV1.2 and Rad, showing that Ser1981 and Ser25/Ser272 are preferentially phosphorylated, with structural insights into PKA's substrate recognition.

This study identifies two KCNQ2 variants causing developmental encephalopathies by constitutively opening the Kv7.2 pore activation gate, leading to gain-of-function effects.

This study uses molecular modeling and simulations to show that N-linked glycans on Nav channel alpha-subunits may block beta-subunit Ig-domain binding and influence channel clustering.

The paper investigates how G-proteins and Ca2+ regulate Cav2.2 N-type Ca2+ channels, showing distinct voltage-dependent facilitation mechanisms for Ba2+ and Ca2+ currents.

The paper investigates how different sodium current modes affect spike regularity and excitability in vestibular ganglion neurons, finding that persistent and resurgent currents differentially influence regular and irregular afferents.

This study shows that mammalian PIEZO1 and PIEZO2 channels rectify chloride currents inwardly, while sodium currents show little rectification, indicating voltage-dependent anion permeation.

This paper introduces a kinetic modeling framework that integrates multiscale simulations and experimental data to quantify biomolecular reaction flux under varying electrochemical conditions.

The paper introduces voltage-clamp protocols for efficiently capturing hERG ion channel kinetics to aid in modeling.

This study investigates two Kir2.1 mutants linked to Andersen-Tawil syndrome, showing they impair channel function through distinct mechanisms, with C154Y causing dominant-negative effects.

This paper develops a method to inhibit L-type CaV1 channels in neurons using opto-chemogenetic tools, showing acute and potent inhibition through membrane-assisted molecular linkage.

This study investigates the proton selectivity and gating mechanism of the lysosomal cation channel TMEM175 using electrophysiology and molecular dynamics simulations.

The paper uses kinetic models to explore how electrical and chemical potentials influence ion transport properties, revealing insights into rectification and saturation mechanisms in ion channels.

The paper identifies structural and molecular differences in the axon initial segment of human fast-spiking interneurons that lower firing thresholds and reduce input-output delay compared to mice.

This study characterizes a human neuronal model of CACNA1A haploinsufficiency, revealing synaptic deficits and increased intrinsic excitability linked to reduced potassium channel function.

The paper demonstrates that ASO therapy targeting KCNT1 reduces seizures in a severe childhood epilepsy condition by normalizing neuronal function in prenatally enriched neurons.

This study investigates the sex-specific effects of NALCN deletion in Drd2-expressing striatal spiny projection neurons, revealing sex differences in excitability and behavior.

The paper identifies the M-current in larval zebrafish primary motoneurons and shows its developmental role in excitability control.

This study identifies a unique sodium permeability in the C. elegans K2P channel UNC-58, driven by an atypical cysteine residue in its selectivity filter, highlighting the need for functional experiments to understand sequence variations in potassium channels.

The paper compares how synaptic potentiation modulates Ih in excitatory and inhibitory hippocampal neurons, finding opposite effects in CA1 pyramidal neurons and sRad interneurons.

This study identifies KV1.8 as essential for distinct potassium conductances in type I and II vestibular hair cells, affecting their electrophysiological properties and function.

The paper investigates how two KCNQ3 mutations impair channel function and shows that polyunsaturated fatty acids can restore wild-type function in these mutations.

This study shows propofol directly binds and inhibits RyR1, reducing Ca2+ release and potentially protecting against malignant hyperthermia.

This study shows glucocorticoids rapidly reduce Kv2.1 and CaV1.2 surface expression in hippocampal neurons, decreasing Ca2+ spikes through endocytosis of Kv2.1 clusters and reduced PKA activity.

This study shows that Mint/PDZ domains from non-bilaterian animals bind CaV2 channel C-termini in vitro, suggesting an ancient interaction with evolutionary changes in binding specificity.