Ion channel regulation and function

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.

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

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.

This paper investigates how the small molecule NS11021 activates BK channels by increasing inner pore hydration through atomistic simulations.

This study investigates how G-proteins inhibit N-type calcium channels by selectively affecting voltage-sensor domains during presynaptic inhibition.

This paper describes a method to rapidly purify ryanodine receptors from small protein samples for cryo-EM, demonstrating its effectiveness by solving receptor structures.

This paper identifies a lower cytoplasmic gate in TALK-2 channels and demonstrates bidirectional coupling between this gate and the selectivity filter gate, showing that ion occupancy and stimuli can influence both gates.

The paper determines structures of conductive and non-conductive HERG selectivity filters and identifies a mechanism for rapid inactivation kinetics.

This study maps disease-associated missense mutations in voltage-gated sodium channels and shows that their effects on channel function are more nuanced than traditional gain-of-function or loss-of-function classifications.

This study determines the cryo-EM structure of LqhIT bound to NavPas, revealing its interaction with a glycan at the pore domain and its mechanism of action.

This study uses molecular dynamics simulations to investigate how two activators affect TREK1 channel gating by modulating hydrogen bond networks and carbonyl flipping in the selectivity filter.

This study examines the biophysical effects of the L360P mutation in Kv2.1/6.4 channels, showing its impact on channel function and providing insights into migraine pathophysiology.

This study shows that cholesterol depletion alters Nav1.7 structure and function, affecting its gating and drug response, with implications for pain management.

The paper examines the evolution of a Na+ binding site in ENaC subunits, showing that the site is conserved in subunits but lost in delta subunits, suggesting divergent roles in Na+ homeostasis.

This paper introduces an optimal experimental design for ion channel gating characterization by efficiently exploring the phase-voltage space using hERG/Kv11.1 currents.

This study shows that Piezo1 conformational changes, not ion permeation, modulate TREK1 K2P channels, suggesting conformational signaling as a potential mechanism.

This study determines the cryo-EM structure of MscS2 from Nematocida displodere, revealing its unique 6-channel super-structure and conservation of bacterial MscS features.

This study uses time-resolved tmFRET to analyze conformational changes and energetics in the SthK C-terminal region upon cAMP and cGMP binding, revealing large structural changes with cAMP and partial agonism with cGMP.

This study investigates N-type and C-type inactivation in the Aplysia Kv1 channel, showing that N-C coupling affects inactivation recovery and that Zn2+ accelerates C-type inactivation.