ArticleProceedings of the National Academy of Sciences of the United States of America2013
Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Coupling of functionality to trafficking of KCNQ2/3 potassium channels at the axon initial segment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mapping the knowledge of epilepsy and Potassium Channels: A scientometric analysis in CiteSpace and VOSviewer.IBRO neuroscience reports · 2025Article
- Phosphoinositide signalling in cell motility and adhesion.Nature cell biology · 2025Review
- Electro-mechanical coupling of KCNQ channels is a target of epilepsy-associated mutations and retigabine.Science advances · 2022Article
- PIPCommunications biology · 2021Article
- Novel KCNQ4 variants in different functional domains confer genotype- and mechanism-based therapeutics in patients with nonsyndromic hearing loss.Experimental & molecular medicine · 2021Article
- Tracking Membrane Protein Dynamics in Real Time.The Journal of membrane biology · 2021Review
- Modulation of KFrontiers in pharmacology · 2020Article
- Gq-Coupled Muscarinic Receptor Enhancement of KCNQ2/3 Channels and Activation of TRPC Channels in Multimodal Control of Excitability in Dentate Gyrus Granule Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Phosphatidylinositol 4,5-bisphosphate (PIPThe Journal of biological chemistry · 2018Article
- One drug-sensitive subunit is sufficient for a near-maximal retigabine effect in KCNQ channels.The Journal of general physiology · 2018Article
- Zinc pyrithione activates K+ channels and hyperpolarizes the membrane of rat pulmonary artery smooth muscle cells.PloS one · 2018Article
- Computational Lipidomics of the Neuronal Plasma Membrane.Biophysical journal · 2017Article
- PIP2 mediates functional coupling and pharmacology of neuronal KCNQ channels.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Chansporter complexes in cell signaling.FEBS letters · 2017Review
- Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Synergistic interplay of Gβγ and phosphatidylinositol 4,5-bisphosphate dictates Kv7.4 channel activity.Pflugers Archiv : European journal of physiology · 2017Article
- Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate.Scientific reports · 2016Article
- The anticonvulsant retigabine suppresses neuronal KScientific reports · 2016Article
- Ion channel regulation by β-secretase BACE1 - enzymatic and non-enzymatic effects beyond Alzheimer's disease.Channels (Austin, Tex.) · 2016Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1-KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4-S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2.
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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.