ArticleThe Journal of pharmacology and experimental therapeutics2017
XE991 and Linopirdine Are State-Dependent Inhibitors for Kv7/KCNQ Channels that Favor Activated Single Subunits.
Article in The Journal of pharmacology and experimental therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Distinct developmental dynamics of opposing persistent currents shape motoneuron firing during motor maturation of zebrafish.The Journal of physiology · 2026Article
- 4-Aminopyridine induced hyperpolarizing oscillations in pediatric human epileptic tissue are network-driven potassium currents that are abolished by activation of KCNQ2-5 (Kv7.2-Kv7.5) channels.Neurobiology of disease · 2026Article
- Increased KCNQ3 expression in papillary thyroid cancer promotes proliferation and migration.Cancer cell international · 2025Article
- A Novel Functional Method of Protector Screening for Zebrafish Lateral Line Hair Cells via the Acoustic Escape Response.Neuroscience bulletin · 2025Article
- Properties of rhythmogenic currents in spinal Shox2 interneurons across postnatal development.The Journal of physiology · 2025Article
- Article
- Sympathetic motor neuron dysfunction is a missing link in age-associated sympathetic overactivity.eLife · 2024Article
- GABA Receptors and KNeurochemical research · 2024Article
- Estradiol elicits distinct firing patterns in arcuate nucleus kisspeptin neurons of females through altering ion channel conductances.bioRxiv : the preprint server for biology · 2024Article
- Sympathetic Motor Neuron Dysfunction is a Missing Link in Age-Associated Sympathetic Overactivity.bioRxiv : the preprint server for biology · 2024Article
- Voltage-gated potassium channels control extended access cocaine seeking: a role for nucleus accumbens astrocytes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Donepezil as a new therapeutic potential in KCNQ2- and KCNQ3-related autism.Frontiers in cellular neuroscience · 2024Article
- rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- Dehydroepiandrosterone Sulfate (DHEAS) Is an Endogenous Kv7 Channel Modulator That Reduces Kv7/M-Current Suppression and Inflammatory Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Site and Mechanism of ML252 Inhibition of Kv7 Voltage-Gated Potassium Channels.Function (Oxford, England) · 2023Article
- Analgesic Action of Acetaminophen via Kv7 Channels.International journal of molecular sciences · 2022Article
- Genetic Knockout of TRPM2 Increases Neuronal Excitability of Hippocampal Neurons by Inhibiting Kv7 Channel in Epilepsy.Molecular neurobiology · 2022Article
- Removal of KCNQ2 from parvalbumin-expressing interneurons improves anti-seizure efficacy of retigabine.Experimental neurology · 2022Article
- Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated KInternational journal of molecular sciences · 2021Article
- The Amyloid Precursor Protein C99 Fragment Modulates Voltage-Gated Potassium Channels.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Article
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3 authors.
Funding
Abstract
M-channel inhibitors, especially XE991, are being used increasingly in animal experiments; however, insufficient characterization of XE991 at times confounds the interpretation of results when using this compound. Here, we demonstrate that XE991 and linopirdine are state-dependent inhibitors that favor the activated-subunit of neuronal Kv7/KCNQ channels. We performed patch-clamp experiments on homomeric Kv7.2 or heteromeric Kv7.2/3 channels expressed in Chinese hamster ovary cells to characterize XE991 and linopirdine. Neither inhibitor was efficacious around the resting membrane potential of cells in physiologic conditions. Inhibition of Kv7.2 and Kv7.2/3 channels by XE991 was closely related with channel activation. When the voltage dependence of activation was left-shifted by retigabine or right-shifted by the mutation, Kv7.2(R214D), the shift in half-activation voltage proportionally coincided with the shift in the half-effective potential for XE991 inhibition. Inhibition kinetics during XE991 wash-in was facilitated at depolarized potentials. Ten-minute washout of XE991 resulted in ∼30% current recovery, most of which was attributed to surface transport of Kv7.2 channels. Linopirdine also exhibited similar inhibition characteristics, with the exception of near- complete current recovery after washout at depolarized potentials. Inhibition kinetics of both XE991 and linopirdine was not as sensitive to changes in voltage as would be predicted by open- channel inhibition. Instead, they were well explained by binding to a single activated subunit. The characteristics of XE991 and linopirdine should be taken into account when these M-channel inhibitors are used in experiments.
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