ArticleThe Journal of general physiology2016
Retigabine holds KV7 channels open and stabilizes the resting potential.
Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- KArchiv der Pharmazie · 2026Review
- Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026Review
- Loose-patch recordings reveal differential Kv7-dependent effects on spontaneous excitatory activity in control and epileptic CA1.Frontiers in neurology · 2026Article
- Emerging targets and translational challenges in treating paclitaxel-induced peripheral neuropathy.Molecular biology reports · 2025Review
- Profiling human iPSC-derived sensory neurons for analgesic drug screening using a multi-electrode array.Cell reports methods · 2025Article
- A Novel Compound QO-83 Alleviates Acute and Chronic Epileptic Seizures in Rodents by Modulating KCNS neuroscience & therapeutics · 2025Article
- Effect of a sensing charge mutation on the deactivation of KV7.2 channels.The Journal of general physiology · 2024Article
- Acute retigabine-induced effects on myelinated motor axons in amyotrophic lateral sclerosis.Pharmacology research & perspectives · 2022Article
- Oxaliplatin Depolarizes the IB4Frontiers in molecular neuroscience · 2021Article
- Molecular Insights Into the Gating Kinetics of the Cardiac hERG Channel, Illuminated by Structure and Molecular Dynamics.Frontiers in pharmacology · 2021Review
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Action potentials in Xenopus oocytes triggered by blue light.The Journal of general physiology · 2020Article
- Hysteretic Behavior in Voltage-Gated Channels.Frontiers in pharmacology · 2020Review
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- Modulation of KFrontiers in pharmacology · 2020Article
- AThe Journal of general physiology · 2018Article
- Inverse Modulation of Neuronal KFrontiers in molecular neuroscience · 2018Article
- Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel's selectivity filter.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Hysteresis in voltage-gated channels.Channels (Austin, Tex.) · 2017Review
- Stabilization of the Activated hERG Channel Voltage Sensor by Depolarization Involves the S4-S5 Linker.Biophysical journal · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine's action remains unknown, previous studies have identified the pore region of KV7 channels as the drug's target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 and O2, with O2 being more stable. The O1 state was reached after short membrane depolarizations, whereas O2 was reached after prolonged depolarization or during steady state at the typical neuronal resting potentials. We also found that activation and deactivation seem to follow distinct pathways, suggesting that the KV7.2/KV7.3 channel activity displays hysteresis. As for the action of Retigabine, we discovered that this agonist discriminates between open states, preferentially acting on the O2 state and further stabilizing it. Based on these findings, we proposed a novel mechanism for the therapeutic effect of Retigabine whereby this drug reduces excitability by enhancing the resting potential open state stability of KV7.2/KV7.3 channels. To address this hypothesis, we used a model for action potential (AP) in Xenopus laevis oocytes and found that the resting membrane potential became more negative as a function of Retigabine concentration, whereas the threshold potential for AP firing remained unaltered.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.