ArticleThe Journal of general physiology2006
State-independent block of BK channels by an intracellular quaternary ammonium.
Article in The Journal of general physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 107 citations in OpenAlex.
- Lipid gating of BK channels and activation mechanism by negatively charged lipids.Communications chemistry · 2026Article
- Dibenzoylmethane, a novel β-diketone pore blocker of large-conductance calcium-activated potassium channel.bioRxiv : the preprint server for biology · 2026Article
- Article
- Lipid-mediated hydrophobic gating in the BK potassium channel.Nature communications · 2025Article
- Disruption of a side portal pathway permits closed-state inactivation by BK β subunit N termini.The Journal of general physiology · 2025Article
- Structural basis of voltage-dependent gating in BK channels.Nature communications · 2025Article
- Electronic Polarization Leads to a Drier Dewetted State for Hydrophobic Gating in the Big Potassium Channel.The journal of physical chemistry letters · 2024Article
- Calcium-gated potassium channel blockade via membrane-facing fenestrations.Nature chemical biology · 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
- Central cavity dehydration as a gating mechanism of potassium channels.Nature communications · 2023Article
- Inner pore hydration free energy controls the activation of big potassium channels.Biophysical journal · 2023Article
- CaInternational journal of molecular sciences · 2023Review
- A gating lever and molecular logic gate that couple voltage and calcium sensor activation to opening in BK potassium channels.Science advances · 2022Article
- Mechanism of use-dependent Kv2 channel inhibition by RY785.The Journal of general physiology · 2022Article
- State-dependent inhibition of BK channels by the opioid agonist loperamide.The Journal of general physiology · 2021Article
- BK Channel Gating Mechanisms: Progresses Toward a Better Understanding of Variants Linked Neurological Diseases.Frontiers in physiology · 2021Review
- Calcium-Activated KHandbook of experimental pharmacology · 2021Article
- Selectivity filter ion binding affinity determines inactivation in a potassium channel.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Hydrophobic dewetting in gating and regulation of transmembrane protein ion channels.The Journal of chemical physics · 2020Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular blockade by quaternary ammonium (QA) molecules of many potassium channels is state dependent, where the requirement for channel opening is evidenced by a time-dependent component of block in the macroscopic record. Whether this is the case for Ca(2+)- and voltage-activated potassium (BK) channels, however, remains unclear. Previous work (Li, W., and R.W. Aldrich. 2004. J. Gen. Physiol. 124:43-57) tentatively proposed a state-dependent, trapping model, but left open the possibility of state-independent block. Here, we found BK channel blockade by a novel QA derivative, bbTBA, was time dependent, raising the possibility of state-dependent, open channel block. Alternatively, the observed voltage dependence of block could be sufficient to explain time-dependent block. We have used steady-state and kinetic measurements of bbTBA blockade in order to discriminate between these two possibilities. bbTBA did not significantly slow deactivation kinetics at potentials between -200 and -100 mV, suggesting that channels can close unhindered by bound bbTBA. We further find no evidence that bbTBA is trapped inside BK channels after closing. Measurements of steady state fractional block at +40 mV revealed a 1.3-fold change in apparent affinity for a 33-fold change in P(o), in striking contrast to the 31-fold change predicted by state-dependent block. Finally, the appearance of a third kinetic component of bbTBA blockade at high concentrations is incompatible with state-dependent block. Our results suggest that access of intracellular bbTBA to the BK channel cavity is not strictly gated by channel opening and closing, and imply that the permeation gate for BK channels may not be intracellular.
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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.