ArticleNature chemical biology2024
Calcium-gated potassium channel blockade via membrane-facing fenestrations.
Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Gating crosstalk in potassium channels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanistical and structural basis of Kv channel inhibition by 4-aminopyridine.bioRxiv : the preprint server for biology · 2026Article
- Atomic structure and plasticity of the CTX-MthK complex investigated by cryo-EM, NMR, and MD simulations.Nature communications · 2026Article
- Lipid trapping slows ball-and-chain inactivation in a calcium-activated potassium channel.Nature communications · 2026Article
- Article
- Hydrophobic and lipid-mediated gating mechanism revealed by low-conductance MthK mutants.bioRxiv : the preprint server for biology · 2026Article
- Applying Entropic Measures, Spectral Analysis, and EMD to Quantify Ion Channel Recordings: New Insights into Quercetin and Calcium Activation of BK Channels.Entropy (Basel, Switzerland) · 2025Article
- Lipid-mediated hydrophobic gating in the BK potassium channel.Nature communications · 2025Article
- Structural basis of voltage-dependent gating in BK channels.Nature communications · 2025Article
- CaProtein science : a publication of the Protein Society · 2025Article
- Repositioning pinacidil and its anticonvulsant and anxiolytic properties in murine models.Scientific reports · 2024Article
- Article
- Single-cell transcriptomic analysis reveals genome evolution in predatory litostomatean ciliates.European journal of protistology · 2024Article
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Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
Abstract
Quaternary ammonium blockers were previously shown to bind in the pore to block both open and closed conformations of large-conductance calcium-activated potassium (BK and MthK) channels. Because blocker entry was assumed through the intracellular entryway (bundle crossing), closed-pore access suggested that the gate was not at the bundle crossing. Structures of closed MthK, a Methanobacterium thermoautotrophicum homolog of BK channels, revealed a tightly constricted intracellular gate, leading us to investigate the membrane-facing fenestrations as alternative pathways for blocker access directly from the membrane. Atomistic free energy simulations showed that intracellular blockers indeed access the pore through the fenestrations, and a mutant channel with narrower fenestrations displayed no closed-state TPeA block at concentrations that blocked the wild-type channel. Apo BK channels display similar fenestrations, suggesting that blockers may use them as access paths into closed channels. Thus, membrane fenestrations represent a non-canonical pathway for selective targeting of specific channel conformations, opening novel ways to selectively drug BK channels.
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Registered trials
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.