Ion channel regulation and function

Combinatorial logic of Nav channels in nociceptor excitability: Different degrees of synergy define distinct neuronal groups

The paper investigates how combinations of Nav1.7 and Nav1.8 channels affect nociceptor excitability, showing that their synergistic effects vary across neuronal subtypes.

Effect of ORL-1 on Cav1.2 calcium channels

This study shows ORL-1 interacts with Cav1.2, reducing its membrane expression without changing its biophysical properties.

Loss of SUR1 and Kir6.2 ATP-sensitive potassium channel subunits produces comparable neuronal excitability and morphine antinociception

This study shows that loss of either SUR1 or Kir6.2 subunits in neurons increases dorsal root ganglion excitability and reduces morphine antinociception in mice.

A Binding Site for CVN293 Reveals a Mechanism for Allosteric Control of THIK-1 K2P Channel Gating

This study identifies the binding site of CVN293 on THIK-1 K2P channel and reveals its allosteric inhibition mechanism through cryoEM structures and functional validation.

Characterizing features of Kv channel activation currents by a minimal-state kinetic model

This paper introduces a minimal-state kinetic model to compare Kv channel activation currents by simplifying complex kinetic schemes and capturing essential features with few parameters.

KCNH1 variants associated with neurodevelopmental disorders exhibit prominent gain-of-function

The paper investigates functional properties of KCNH1 variants linked to neurodevelopmental disorders, finding most exhibit gain-of-function characteristics.

Insights on the effect of extracellular acidification on an HCNchannel: a molecular dynamics study

This study uses molecular dynamics simulations to investigate how extracellular acidification affects the structure and function of HCN2 channels by disrupting hydrogen bond networks involving residue E212.

Voltage versus concentration in ion channels: Physical signatures reveal rate-limiting steps

The paper links experimentally observed ion flux with microscopic mechanistic properties of ion channels by analyzing how voltage and chemical potential affect transport, identifying the rate-limiting step.

Modulation of human dorsal root ganglion neuron excitability by Nav1.7 inhibition

This study compares the effects of Nav1.7 and Nav1.8 inhibitors on human dorsal root ganglion neuron excitability, finding Nav1.7 inhibition has larger effects on action potential threshold and upstroke velocity but less impact on repetitive firing.

Computational assay of hERG ion permeation and its modulation by small-molecule compounds

This study uses molecular dynamics simulations to investigate hERG ion permeation and how small molecules modulate it, revealing structural mechanisms and binding modes.

So similar, yet so different: α-synuclein recognition of the isoform-specific VDAC protein-lipid interface

The paper investigates how α-synuclein interacts differently with VDAC isoforms by analyzing binding kinetics and translocation behavior in planar lipid membranes.

An integrated database of ion channels

The paper introduces IDIC, a database integrating information on human ion channels and their disease associations, providing annotations and cross-references to biological resources.

GAT1508, a selective neuronal GIRK1/2 activator, exhibits superior antiepileptic efficacy and synergizes with cannabidiol

This study characterizes GAT1508, a selective neuronal GIRK1/2 activator, showing superior antiepileptic efficacy and synergy with CBD.

A chemical perturbation scan on a K2P channel modulator pocket identifies affinity hotspots

The paper identifies affinity hotspots in the modulator pocket of the K2P channel TREK1 by analyzing chemical substitutions and their effects on binding and gating.

Positive selection and structural disruption of KCNA5 by mutation in colorectal cancer

The paper identifies KCNA5 mutations under positive selection in colorectal cancer and shows they disrupt channel structure and function, affecting tumor pathways.

ATP1A3 E815K Disrupts Sodium Homeostasis and Excitability in Human Alternating Hemiplegia of Childhood Neurons

This study investigates the impact of the ATP1A3 E815K mutation on human neurons, showing disrupted sodium homeostasis and altered excitability.

An AI-Enabled Translational Drug Discovery Framework for NALCN Channelopathy: From High-Throughput Screening to Therapeutic Candidate

This paper develops an AI-driven drug discovery framework for NALCN channelopathy, identifying aprepitant as a lead therapeutic candidate through HTS, structural modeling, and experimental validation.

A permeable G310 constriction limits K+ flux in the activated KCNQ2 pore and is disrupted by the encephalopathy variant G310S

This study identifies G310 as the flux-limiting constriction in the activated KCNQ2 pore and shows the G310S variant reduces K+ conduction by altering the water column and ion movement.

Activation pathway of the human voltage-gated proton channel

This study determines the activation pathway of the human voltage-gated proton channel hHV1 using computational methods, revealing voltage-driven structural changes and lipid effects validated by experiments.

4-methyl-3-aminopyridine: A novel active blocker of voltage-gated potassium ion channels in the central nervous system.

This study characterizes 4-methyl-3-aminopyridine as a potent KV channel blocker with improved pharmacological properties compared to 4-aminopyridine.

Stoichiometry-dependent gating and structural pharmacology of cardiac GIRK1/4 channels

The paper reports structures of GIRK1/4 channels with different stoichiometries and shows how subunit composition affects ligand binding and pharmacology.

Asymmetric assembly underlies activation mechanism of neuronal GIRK1/2 channels

This study reveals how asymmetric assembly of GIRK1/2 channels couples lipid-dependent gating to K+ permeation and pharmacological activation through structural and functional analyses.

Lipid gating of BK channels and mechanism of activation by negatively charged lipids

This study investigates how lipid interactions influence BK channel conductivity and activation, proposing a multi-modal mechanism involving lipid entry reduction and structural stabilization.

L-type channel voltage-dependent facilitation results from asymmetric π-H and π-π quadrangle interactions at DI-DII domains

This study identifies asymmetric π-H and π-π quadrangle interactions at the DI-DII interface of L-type channels as the molecular basis for voltage-dependent facilitation.

Fast Diffusion of Bound Ca: Analytical and Experimental Characterization of One- and Two-Dimensional Traveling Waves

The paper develops an analytical framework for reaction diffusion equations in Ca nanodomains, showing that Ca bound buffers and sensors propagate as traveling waves, supported by experimental measurements.

The structural dynamics and molecular coupling in the slow inactivation of a prokaryotic voltage-gated sodium channel

This study uses smFRET to reveal conformational changes in the prokaryotic NavAb channel during slow inactivation, identifying key residues that coordinate structural transitions.

Mitochondrial ATP-dependent K+ channels downregulate ionotropic glutamate receptors during hypoxia in retinal horizontal cells of goldfish

This study shows that hypoxia reduces ionotropic glutamate receptor activity in goldfish retinal horizontal cells via mitochondrial ATP-sensitive K+ channels and intracellular calcium signaling.

MgATP/MgADP-dependent conformational dynamics and intrinsically disordered regions of vascular KATP channels revealed by cryoEM

This study uses cryoEM to reveal MgATP/MgADP-dependent conformational changes and IDR organization in vascular KATP channels.

Computational Framework for Identifying Ion Channel Mutation-Compensating Interventions

The paper presents a computational framework to identify interventions that compensate for ion channel mutations by modulating other conductances, demonstrating feasibility through simulations and a differentiable Hodgkin-Huxley model.

Structural basis for differential inhibition of THIK1 by chemically related inhibitors

This study determines the structural basis for differential inhibition of THIK1 by chemically related inhibitors using cryo-EM, showing how they affect different gates despite sharing a common binding site.