ArticleThe Journal of general physiology2020
Molecular mechanism of BK channel activation by the smooth muscle relaxant NS11021.
Article in The Journal of general physiology, 2020. 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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27 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Dibenzoylmethane, a novel β-diketone pore blocker of large-conductance calcium-activated potassium channel.bioRxiv : the preprint server for biology · 2026Article
- Tuning the gate and the gear: The LRRC26 (γ1) subunit modulates intrinsic gating and voltage-sensor coupling of the BK channel.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- 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
- Tuning the gate and the gear: The LRRC26 (bioRxiv : the preprint server for biology · 2025Article
- Lipid-mediated hydrophobic gating in the BK potassium channel.Nature communications · 2025Article
- Small Molecule NS11021 Promotes BK Channel Activation by Increasing Inner Pore Hydration.Journal of chemical information and modeling · 2024Article
- Activation mechanism and novel binding sites of the BKLife science alliance · 2024Article
- Structural mapping of patient-associated KCNMA1 gene variants.Biophysical journal · 2024Article
- Loss of anoctamin 1 reveals a subtle role for BK channels in lymphatic muscle action potentials.The Journal of physiology · 2024Article
- Lysosomal BK channels facilitate silica-induced inflammation in macrophages.Inhalation toxicology · 2024Article
- Inner pore hydration free energy controls the activation of big potassium channels.Biophysical journal · 2023Article
- An allosteric modulator activates BK channels by perturbing coupling between CaNature communications · 2022Article
- Novel Thioxothiazolo[3,4-ACS medicinal chemistry letters · 2022Article
- The AMIGO1 adhesion protein activates Kv2.1 voltage sensors.Biophysical journal · 2022Article
- Alternative Targets for Modulators of Mitochondrial Potassium Channels.Molecules (Basel, Switzerland) · 2022Review
- BK Channel in the Physiology and in the Cancer of Pancreatic Duct: Impact and Reliability of BK Openers.Frontiers in pharmacology · 2022Review
- Article
- State-dependent inhibition of BK channels by the opioid agonist loperamide.The Journal of general physiology · 2021Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
Large-conductance Ca2+-activated K+ channels (BK channels) are activated by cytosolic calcium and depolarized membrane potential under physiological conditions. Thus, these channels control electrical excitability in neurons and smooth muscle by gating K+ efflux and hyperpolarizing the membrane in response to Ca2+ signaling. Altered BK channel function has been linked to epilepsy, dyskinesia, and other neurological deficits in humans, making these channels a key target for drug therapies. To gain insight into mechanisms underlying pharmacological modulation of BK channel gating, here we studied mechanisms underlying activation of BK channels by the biarylthiourea derivative, NS11021, which acts as a smooth muscle relaxant. We observe that increasing NS11021 shifts the half-maximal activation voltage for BK channels toward more hyperpolarized voltages, in both the presence and nominal absence of Ca2+, suggesting that NS11021 facilitates BK channel activation primarily by a mechanism that is distinct from Ca2+ activation. 30 µM NS11021 slows the time course of BK channel deactivation at -200 mV by ∼10-fold compared with 0 µM NS11021, while having little effect on the time course of activation. This action is most pronounced at negative voltages, at which the BK channel voltage sensors are at rest. Single-channel kinetic analysis further shows that 30 µM NS11021 increases open probability by 62-fold and increases mean open time from 0.15 to 0.52 ms in the nominal absence of Ca2+ at voltages less than -60 mV, conditions in which BK voltage sensors are largely in the resting state. We could therefore account for the major activating effects of NS11021 by a scheme in which the drug primarily shifts the pore-gate equilibrium toward the open state.
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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.