Ion channel regulation and function

Volatile anaesthetics modulate voltage-gated sodium channel function at a site critical for gating

This study identifies a volatile anaesthetic binding site in voltage-gated sodium channels, showing it modulates channel function and reduces neuronal excitability.

Differential Assembly of Native ENaC Complexes Across Mouse Epithelial Tissues

This study uses a knock-in mouse model to analyze native ENaC complexes in different tissues, revealing tissue-specific differences in channel abundance and complex size.

Dynamic single-molecule binding of carbamazepine explains diffuse cryo-EM density in the SUR1 drug-binding pocket

The paper investigates the diffuse cryo-EM density of carbamazepine in the SUR1 drug-binding pocket and finds it results from dynamic single-molecule binding rather than dimerization.

APpar: automated action potential parameter analysis software for reproducible electrophysiological measurements in neurons

APpar automates action potential parameter extraction in neuronal electrophysiology, improving reproducibility through threshold validation and standardized measurements.

Hill-Based Reformulation of the Hodgkin-Huxley Model for Mapping Gating Changes to Neuronal Excitability

The paper reformulates the Hodgkin-Huxley model using a Hill-based approach to map gating changes to neuronal excitability under limited kinetic data.

Ion channel and receptor-mediated regulation of axonal conduction reliability in sympathetic preganglionic neurons.

The paper investigates axonal conduction reliability in sympathetic preganglionic neurons, showing it is modifiable and regulated by ion channels and receptors.

A hERG Blocker Facilitates K+ Channel Current by Agonizing Pore Opening while Blocking

The paper investigates how hERG blockers like nifekalant can increase K+ channel current through an agonism-while-blocking mechanism, potentially explaining their safety profile.

Cholesterol, PtdIns(4,5)P2, and Actin Regulate BK Channel Nanoscale Organization

This study investigates how cholesterol, PtdIns(4,5)P2, and actin regulate BK channel nanoscale organization using super-resolution imaging and FRAP in heterologous and endogenous systems.

Structural basis for proton inhibition of the two-pore domain K+ channel TASK-1

This study determines the cryo-EM structure of TASK-1 at low pH and shows how protonation of an extracellular histidine leads to channel closure, with mutations affecting proton sensitivity.

Intersectional CRISPR-Cas9 genetic targeting reveals acute role of Nav1.1 in proprioceptive behavior and function

This study uses an intersectional CRISPR-Cas9 approach to target NaV1.1 in proprioceptors, revealing its essential role in motor coordination and action potential firing.

Proteostatic significance of helix O alanine residues in CLC channels

This study examines the role of helix O alanine residues in CLC channels, showing that mutations at these sites cause proteostatic defects and impair channel function.

Conformational changes upon pore blocker removal reveal conductive states of TMEM16A

The paper uses molecular dynamics simulations and electrophysiology to study conformational changes in TMEM16A upon inhibitor removal, revealing conductive and non-conductive states and mechanisms of Ca2+-dependent gating.

Pathways regulating the excitability of sympathetic neurons derived from human induced pluripotent stem cells

This paper uses hiPSC-derived sympathetic neurons to study pathways regulating neuronal excitability and finds that GIRK channels mediate inhibitory effects of adrenergic and muscarinic receptors.

Gating effects of a Cav2.3 calcium channel mutation linked to developmental and epileptic encephalopathy

This study examines the biophysical effects of a Cav2.3 channel mutation (L228P) linked to DEEs using whole-cell patch-clamp, finding a shift in voltage-dependent activation and inactivation towards hyperpolarized potentials.

Genetically engineered rapamycin responsive K2P channels

This paper genetically engineers K2P channels to be activated by rapamycin or its analogs, enabling chemogenetic control of cellular membrane potential.

Evolutionary analysis of vertebrate KCNH voltage-gated potassium channels and their expression in zebrafish embryos

The paper analyzes the evolutionary history and embryonic expression of KCNH voltage-gated potassium channels in zebrafish, revealing their origins in invertebrates and expanded gene numbers in vertebrates.

A unified ensemble-allosteric framework reconciles gain- and loss-of-function disease mutations in the IP3 receptor

This paper develops a unified ensemble-allosteric framework to explain how gain- and loss-of-function mutations in IP3R1 cause disease by altering conformational dynamics and allosteric communication.

MILDEW RESISTANCE LOCUS O (MLO) proteins function as trimeric inward calcium channels

This study identifies MLO proteins as trimeric inward calcium channels, revealing their structural and functional mechanisms for calcium influx in plants.

Identification and classification of ion-channels across the tree of life provide functional insights into understudied CALHM channels

The paper identifies and classifies ion channels across species, revealing functional insights into understudied CALHM channels through sequence, structure, and functional data integration.

Electrodiffusion analysis of concentration and voltage changes in thin cylindrical domains using cross-diffusion modelling

This paper derives analytic current-voltage-concentration relations for narrow cylindrical domains using cross-diffusion equations, showing how ion influx affects voltage and other ions' concentrations.

Down- to up-state transition is the default pathway in TREK K2P channel activation and does not involve a lipid occluded pore

The paper identifies the down-to-up state transition as the primary activation pathway for TREK K2P channels, showing it does not involve lipid occlusion of the pore.

In vivo characterization of a patient CACNA1A variant reveals paradoxical synaptic effects

The paper characterizes a CACNA1A variant in a patient with mixed clinical symptoms, showing conflicting in vitro and in vivo effects that highlight the importance of cellular context.

Biochemical assessment of α-α-subunit interactions of Nav1.5 in a heterologous expression system

This study assesses α-α-subunit interactions of Nav1.5 in a heterologous expression system and finds that interactions depend on N-linked glycosylation and non-native disulfide bonds.

Lipid bilayers determine the allostery but not intrinsic affinity of cAMP binding to pacemaker channels

This study shows lipid bilayers enable cooperative cAMP binding to HCN channels but do not affect intrinsic binding affinity, revealing a role for membranes in enhancing inter-subunit interactions.

Blood Pressure Regulates Functional Coupling of L-Type Ca2+ Channels: Reimaging the Foundation of Cerebral Blood Flow Control.

This study identifies a pressure-sensitive regulatory mechanism of L-type Ca2+ channels that influences cerebral blood flow control and cognitive function.

Protection against diet-induced obesity by a single-point mutation in Kir2.1 channels

This study shows that a single-point mutation in Kir2.1 channels protects mice from diet-induced obesity by altering fat distribution and increasing energy expenditure.

Hydrophobic and lipid-mediated gating mechanism revealed by low-conductance MthK mutants

This study investigates the gating mechanism of MthK channels using mutants, revealing hydrophobic and lipid-mediated processes that drive channel closure.

Interrogating the structure and function of the human voltage-gated proton channel (hHv1) with a fluorescent noncanonical amino acid.

This study uses fluorescent noncanonical amino acids to measure conformational changes in hHv1, showing Zn2+ induces reversible FRET changes.

Calcium-dependent facilitation of P/Q-type calcium channels governs the polarity and magnitude of short-term synaptic plasticity

This study shows that calcium-dependent facilitation of P/Q-type calcium channels controls the polarity and magnitude of short-term synaptic plasticity in fast-spiking synapses.

Dibenzoylmethane, a novel β-diketone pore blocker of large-conductance calcium-activated potassium channel

This study identifies dibenzoylmethane (DBM) as a novel inhibitor of BKCa channels, showing it blocks the pore and alters ion dynamics, with structural features critical for activity.