ArticleProceedings of the National Academy of Sciences of the United States of America2015
Molecular mechanisms underlying the effect of the novel BK channel opener GoSlo: involvement of the S4/S5 linker and the S6 segment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Article
- The BK channel-NS1619 agonist complex reveals molecular insights into allosteric activation gating.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Computational Ligand-Binding Site Prediction.Advances in experimental medicine and biology · 2026Review
- Positive allosteric modulation of emodepside sensitive Brugia malayi SLO-1F and Onchocerca volvulus SLO-1A potassium channels by GoSlo-SR-5-69.PLoS pathogens · 2025Article
- Pulmonary Circulation Under Pressure: Pathophysiological and Therapeutic Implications of BK Channel.Cardiovascular drugs and therapy · 2025Review
- Activation mechanism and novel binding sites of the BKLife science alliance · 2024Article
- Subunit-specific inhibition of BK channels by piperine.Biophysical journal · 2024Article
- Incorporating physics to overcome data scarcity in predictive modeling of protein function: A case study of BK channels.PLoS computational biology · 2023Article
- Incorporating physics to overcome data scarcity in predictive modeling of protein function: a case study of BK channels.bioRxiv : the preprint server for biology · 2023Article
- BK channel modulation by positively charged peptides and auxiliary γ subunits mediated by the Ca2+-bowl site.The Journal of general physiology · 2023Article
- Calcium-Activated KHandbook of experimental pharmacology · 2021Article
- Differential regulation of BK channels by fragile X mental retardation protein.The Journal of general physiology · 2020Article
- Molecular mechanism of BK channel activation by the smooth muscle relaxant NS11021.The Journal of general physiology · 2020Article
- Vasodilation of rat skeletal muscle arteries by the novel BK channel opener GoSlo is mediated by the simultaneous activation of BK and KBritish journal of pharmacology · 2020Article
- LINGO1 is a regulatory subunit of large conductance, CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Differential efficacy of GoSlo-SR compounds on BKα and BKαγChannels (Austin, Tex.) · 2017Article
- Tagging of Endogenous BK Channels with a Fluorogen-Activating Peptide Reveals β4-Mediated Control of Channel Clustering in Cerebellum.Frontiers in cellular neuroscience · 2017Article
- Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders.Pharmacological reviews · 2016Review
- 2014 Conway review lecture, Royal Academy of Medicine in Ireland: “S6, drugs and RCK and Bowl”.Irish journal of medical science · 2016Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GoSlo-SR-5-6 is a novel large-conductance Ca(2+)-activated K(+) (BK) channel agonist that shifts the activation V1/2 of these channels in excess of -100 mV when applied at a concentration of 10 μM. Although the structure-activity relationship of this family of molecules has been established, little is known about how they open BK channels. To help address this, we used a combination of electrophysiology, mutagenesis, and mathematical modeling to investigate the molecular mechanisms underlying the effect of GoSlo-SR-5-6. Our data demonstrate that the effects of this agonist are practically abolished when three point mutations are made: L227A in the S4/S5 linker in combination with S317R and I326A in the S6C region. Our data suggest that GoSlo-SR-5-6 interacts with the transmembrane domain of the channel to enhance pore opening. The Horrigan-Aldrich model suggests that GoSlo-SR-5-6 works by stabilizing the open conformation of the channel and the activated state of the voltage sensors, yet decouples the voltage sensors from the pore gate.
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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.