ArticleThe Journal of biological chemistry2008
Desensitization of chemical activation by auxiliary subunits: convergence of molecular determinants critical for augmenting KCNQ1 potassium channels.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Centipede Venom Peptides Acting on Ion Channels.Toxins · 2020Pooled it
- Electro-Mechanical Uncoupling of KArchiv der Pharmazie · 2026Article
- A mechanistic understanding of how KCNE1 tunes KCNQ1 channel pharmacology.Structure (London, England : 1993) · 2026Article
- Graded activation of mutant K41C-KCNE1:KCNQ1 channel complexes by mefenamic acid.Channels (Austin, Tex.) · 2025Article
- IBiomedicines · 2023Article
- Structural mechanisms for the activation of human cardiac KCNQ1 channel by electro-mechanical coupling enhancers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277.Nature communications · 2022Article
- ML277 regulates KCNQ1 single-channel amplitudes and kinetics, modified by voltage sensor state.The Journal of general physiology · 2021Article
- Chemical modulation of Kv7 potassium channels.RSC medicinal chemistry · 2021Review
- Pharmacological Activation of Neuronal Voltage-Gated Kv7/KCNQ/M-Channels for Potential Therapy of Epilepsy and Pain.Handbook of experimental pharmacology · 2021Article
- Article
- ML277 specifically enhances the fully activated open state of KCNQ1 by modulating VSD-pore coupling.eLife · 2019Article
- Deconstruction of an African folk medicine uncovers a novel molecular strategy for therapeutic potassium channel activation.Science advances · 2018Article
- KCNE1 tunes the sensitivity of KeLife · 2018Article
- Zinc pyrithione activates K+ channels and hyperpolarizes the membrane of rat pulmonary artery smooth muscle cells.PloS one · 2018Article
- Effects of protein-protein interactions and ligand binding on the ion permeation in KCNQ1 potassium channel.PloS one · 2018Article
- Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.Cardiac electrophysiology clinics · 2016Review
- KCNQ1 channel modulation by KCNE proteins via the voltage-sensing domain.The Journal of physiology · 2015Review
- Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Probing binding sites and mechanisms of action of an I(Ks) activator by computations and experiments.Biophysical journal · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Chemical openers for KCNQ potassium channels are useful probes both for understanding channel gating and for developing therapeutics. The five KCNQ isoforms (KCNQ1 to KCNQ5, or Kv7.1 to Kv7.5) are differentially localized. Therefore, the molecular specificity of chemical openers is an important subject of investigation. Native KCNQ1 normally exists in complex with auxiliary subunits known as KCNE. In cardiac myocytes, the KCNQ1-KCNE1 (IsK or minK) channel is thought to underlie the I(Ks) current, a component critical for membrane repolarization during cardiac action potential. Hence, the molecular and pharmacological differences between KCNQ1 and KCNQ1-KCNE1 channels have been important topics. Zinc pyrithione (ZnPy) is a newly identified KCNQ channel opener, which potently activates KCNQ2, KCNQ4, and KCNQ5. However, the ZnPy effects on cardiac KCNQ1 potassium channels remain largely unknown. Here we show that ZnPy effectively augments the KCNQ1 current, exhibiting an increase in current amplitude, reduction of inactivation, and slowing of both activation and deactivation. Some of these are reminiscent of effects by KCNE1. In addition, neither the heteromultimeric KCNQ1-KCNE1 channels nor native I(Ks) current displayed any sensitivity to ZnPy, indicating that the static occupancy by a KCNE subunit desensitizes the reversible effects by a chemical opener. Site-directed mutagenesis of KCNQ1 reveals that residues critical for the potentiation effects by either ZnPy or KCNE are clustered together in the S6 region overlapping with the critical gating determinants. Thus, the convergence of potentiation effects and molecular determinants critical for both an auxiliary subunit and a chemical opener argue for a mechanistic overlap in causing potentiation.
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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.