xe-991--anthracenone has been researched along with Seizures* in 2 studies
2 other study(ies) available for xe-991--anthracenone and Seizures
Article | Year |
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Event-Associated Oxygen Consumption Rate Increases ca. Five-Fold When Interictal Activity Transforms into Seizure-Like Events In Vitro.
Topics: Action Potentials; Adenosine Triphosphate; Animals; Anthracenes; Bicuculline; Electrophysiology; Flavin-Adenine Dinucleotide; Male; Oxygen Consumption; Rats; Rats, Wistar; Seizures | 2017 |
M-current preservation contributes to anticonvulsant effects of valproic acid.
Valproic acid (VPA) has been widely used for decades to treat epilepsy; however, its mechanism of action remains poorly understood. Here, we report that the anticonvulsant effects of nonacute VPA treatment involve preservation of the M-current, a low-threshold noninactivating potassium current, during seizures. In a wide variety of neurons, activation of Gq-coupled receptors, such as the m1 muscarinic acetylcholine receptor, suppresses the M-current and induces hyperexcitability. We demonstrated that VPA treatment disrupts muscarinic suppression of the M-current and prevents resultant agonist-induced neuronal hyperexcitability. We also determined that VPA treatment interferes with M-channel signaling by inhibiting palmitoylation of a signaling scaffold protein, AKAP79/150, in cultured neurons. In a kainate-induced murine seizure model, administration of a dose of an M-channel inhibitor that did not affect kainate-induced seizure transiently eliminated the anticonvulsant effects of VPA. Retigabine, an M-channel opener that does not open receptor-suppressed M-channels, provided anticonvulsant effects only when administered prior to seizure induction in control animals. In contrast, treatment of VPA-treated mice with retigabine induced anticonvulsant effects even when administered after seizure induction. Together, these results suggest that receptor-induced M-current suppression plays a role in the pathophysiology of seizures and that preservation of the M-current during seizures has potential as an effective therapeutic strategy. Topics: A Kinase Anchor Proteins; Action Potentials; Animals; Anthracenes; Anticonvulsants; Carbamates; Cells, Cultured; Drug Interactions; Female; Hippocampus; Humans; Kainic Acid; KCNQ2 Potassium Channel; Lipoylation; Male; Mice; Mice, Inbred C57BL; Muscarinic Agonists; Muscarinic Antagonists; Neurons; Phenylenediamines; Phosphorylation; Potassium Channel Blockers; Protein Processing, Post-Translational; Rats; Receptor, Muscarinic M1; Recombinant Fusion Proteins; Seizures; Signal Transduction; Superior Cervical Ganglion; Valproic Acid | 2015 |