Ion channel regulation and function

Structural and Functional Mechanisms Underlying Activation Gate Dynamics and IFM Motif Accessibility in Human Nav1.5

This study presents a cryo-EM structure of human Nav1.5 in an intermediate open state, revealing a new Na+ binding site and showing ion binding modulates IFM motif docking and inactivation kinetics.

Modeling Fast CICI Calcium Waves

The paper proposes a mathematical model of fast calcium induced calcium influx (CICI) waves, explaining their high propagation speed through mechanochemical interactions in the actomyosin network.

Energetic cross-talk of filter gate and lower helices drives polymodal regulation and disease in TREK K2P channels

This study uses molecular dynamics to analyze TREK-2 channel conformational changes, linking them to disease mechanisms and drug discovery.

Molecular dynamics of the pathogenic KCNQ2 variant G256W reveal mechanisms of channel dysfunction in epileptic encephalopathy

The paper uses molecular dynamics simulations to analyze the KCNQ2 G256W variant, revealing structural changes in the pore domain that disrupt ion selectivity and contribute to epileptic encephalopathy.

Selectivity Filter Dynamics Define Ion Conductance and Selectivity Differences in CNG and HCN Channels

This study uses molecular dynamics simulations to compare ion conduction mechanisms in HCN and CNG channels, revealing differences in selectivity filter dynamics that explain their functional divergence.

Structure-function analysis of lithium-ion selectivity of voltage-gated sodium channel

This study identifies the molecular basis of lithium-ion selectivity in voltage-gated sodium channels through mutagenesis, electrophysiology, and crystallography.

Two-step voltage-sensor activation of the human KV7.4 channel and effect of a deafness-associated mutation

This study investigates the two-step voltage-sensor activation mechanism of the KV7.4 channel and shows how a deafness mutation disrupts this process.

A silent Kv channel subunit shapes PV neuron action potential waveform and short-term synaptic plasticity during high-frequency firing

This paper identifies Kv6.4 as a PV neuron-specific Kv channel subunit that modulates action potential waveform and synaptic plasticity during high-frequency firing.

Conformational landscape and clustering of human type 2 IP3 receptor in lipid nanodiscs

The paper determines cryo-EM structures of human IP3R-2 in different conformations and clusters, revealing ligand interactions and subtype-specific features.

Insights into the structure and modulation of human TWIK-2

This study presents the cryo-EM structure of human TWIK-2 and identifies key residues and modulators, providing a foundation for developing anti-inflammatory therapeutics.

From Flux to Function: Extracting Mechanistic Insights from Ion Channels via I-V and I-μ Analyses

This paper develops a mathematical framework to relate ion channel properties to I-V and I-μ relationships, revealing mechanistic insights into open-channel flux and rectification.

The BK channel-NS1619 agonist complex reveals molecular insights on allosteric activation gating

The paper identifies how NS1619 binds to BK channels and stabilizes their open conformation through structural and dynamic analysis.

Structural dynamics of adenine nucleotide potentiation of the human type 2 IP3 receptor

This study investigates how adenine nucleotides potentiate human type 2 IP3R activity by rigidifying the juxtamembrane domain through structural and computational analysis.

Oxidant-mediated activation and inhibition of LRRC8C and LRRC8D channel currents require N-terminal and Transmembrane 1 pore domains

This study identifies N-terminal and transmembrane domain regions in LRRC8C and LRRC8D channels that mediate oxidant-dependent current activation and inhibition.

Calcium interaction with Nav1.5 via FGF12A and CaM binding

This study investigates how calcium regulates Nav1.5 inactivation through interactions with CaM and FGF12A, showing a Ca2+-dependent shift in steady-state inactivation.

Preferential vulnerability of cortical GABAergic interneurons to Nalcn deficiency

This study shows that NALCN deficiency preferentially affects GABAergic interneurons, reducing their intrinsic excitability and impairing contextual adaptation and spatial memory in mice.

HCN channels reveal conserved and divergent physiology in supragranular pyramidal neurons in primate species

The paper examines HCN-channel properties in primate supragranular pyramidal neurons, finding conserved traits across species with some divergence in magnitude between humans and macaques.

Divalent cation depletion enhances neuronal excitability through CaSR-dependent modulation of threshold channels

This study shows that reducing external calcium or magnesium ions increases neuronal excitability via CaSR-dependent modulation of Kv1 and Nav1.2 channels.

Molecular mechanism of exchange coupling in CLC chloride/proton antiporters

The paper provides a mechanistic model for the 2:1 Cl-/H+ exchange in CLC transporters using structural and computational methods.

Role of Water Models in Simulations of Ion Conduction in Potassium Channels

The paper uses molecular dynamics simulations to show that both hard and soft knock-on mechanisms of ion conduction in potassium channels are accessible and reversible, depending on simulation parameters.

Inhibition mechanism of pancreatic KATP channels by centipede toxins

This paper identifies centipede toxins SpTx1 and Sm3a as inhibitors of human pancreatic KATP channels, revealing their binding mechanism and therapeutic potential for neonatal diabetes.

Membrane potential bistability in human breast cancer MDA-MB-231 cells: A 'Hodgkin-Huxley type' model

The paper develops a Hodgkin-Huxley-type model of membrane potential bistability in MDA-MB-231 breast cancer cells, showing how ion channels and calcium dynamics drive voltage transients.

A pain-reducing Kv6.4 variant spares other Kv6 channels, offering a target for uterine pain

The paper identifies a Kv6.4 variant that selectively reduces function without affecting other Kv6 subunits, suggesting it as a therapeutic target for uterine pain.

Neuronal activity induces myelin voltage changes that reflect action potential dependent myelin potassium buffering

The paper uses genetically encoded voltage indicators to show that myelin depolarizes during neuronal activity, mediated by potassium channels, supporting axonal firing precision.

The expression level of CACNA1C-encoded CaV1.2 is a tipping point between promotion and inhibition of dendritic growth in neurons

The paper shows that CaV1.2 expression level determines whether calcium currents promote or inhibit dendritic growth in neurons, with implications for psychiatric disorders.

Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944

This study investigates the effects of ML218 and Z944 on Cav1.4 channels, finding they inhibit Cav1.4 with lower IC50 values than Cav1.2 and highlight the role of methionine residues in ML218's mechanism.

Assembly and lipid-gating of LRRC8A:D volume-regulated anion channels

This study determines the structure of LRRC8A:D VRACs using cryo-EM, revealing lipid-gating and subunit-specific structural features.

A conserved cytoplasmic glutamic acid mediates pH-dependent gating in bacterial urea channel UreI

This study identifies a conserved cytoplasmic glutamic acid in UreI channels that mediates pH-dependent gating, challenging the notion that periplasmic residues are the sole pH sensors.

KCNK18 c.1107del frameshift in peripheral neuropathy links TRESK dysfunction to neuropathic pain

The paper identifies a frameshift mutation in KCNK18 causing TRESK dysfunction, linking it to neuropathic pain through haploinsufficiency and altered channel function.

Characterization of the functional and clinical impacts of CACNA1A missense variants found in neurodevelopmental disorders

This study analyzes 42 de novo CACNA1A missense variants in neurodevelopmental disorders, finding most alter channel function and correlate with clinical outcomes.