Article

Ethosuximide: subunit- and Gβγ-dependent blocker and reporter of allosteric changes in GIRK channels

2024-06-05

Abstract excerpt

The antiepileptic drug ethosuximide (ETX) suppresses epileptiform activity in a mouse model of GNB1 syndrome, caused by mutations in Gβ 1 protein, likely through the inhibition of G-protein gated K + (GIRK) channels. Here we show that ETX is a subunit-selective, allosteric blocker of GIRKs. The potency of ETX block is increased by the G protein subunit dimer Gβγ, the physiological activator of GIRKs. Molecular...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 461deec3-784a-5c18-bbe0-d7af518ff71d
DOI: 10.1101/2024.06.04.597296

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Ethosuximide: subunit- and Gβγ-dependent blocker and reporter of allosteric changes in GIRK channelsDOI 10.1101/2024.06.04.597296Read

G protein-coupled potassium channels implicated in mouse and cellular models of GNB1 EncephalopathySemantic proximity Read

Key residue Unlocks Dual PIP <sub>2</sub> -Dependent and Independent Gating in G Protein-Gated Inwardly Rectifying Potassium ChannelsSemantic proximity Read

GIRK Channel Loss of Function Increases Dendritic Excitability in a Mouse Model of GNB1 EncephalopathySemantic proximity Read

Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium.Semantic proximity Read

Critical determinants of the G protein gamma subunits in the Gbetagamma stimulation of G protein-activated inwardly rectifying potassium (GIRK) channel activity.Semantic proximity Read

Overexpressing wild-type γ2 subunits rescued the seizure phenotype in Gabrg2+/Q390X Dravet syndrome mice.Semantic proximity Read

Interaction of G protein beta subunit with inward rectifier K(+) channel Kir3.Semantic proximity Read

The small molecule GAT1508 activates brain-specific GIRK1/2 channel heteromers and facilitates conditioned fear extinction in rodents.Semantic proximity Read

Distinct sites on G protein beta gamma subunits regulate different effector functions.Semantic proximity Read

Modulating Endoplasmic Reticulum Chaperones and Mutant Protein Degradation in GABRG2(Q390X) Associated with Genetic Epilepsy with Febrile Seizures Plus and Dravet Syndrome.Semantic proximity Read

Differential protein structural disturbances and suppression of assembly partners produced by nonsense GABRG2 epilepsy mutations: implications for disease phenotypic heterogeneity.Semantic proximity Read

Altered GABAA receptor expression in brainstem nuclei and SUDEP in Gabrg2(+/Q390X) mice associated with epileptic encephalopathy.Semantic proximity Read