ArticleThe Journal of biological chemistry2010
Allosteric block of KCa2 channels by apamin.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 94 citations in OpenAlex.
- Further Investigations on Natural and Synthetic Bis-(1,2,3,4-tetrahydroisoquinoline) Derivatives Interacting with the Apamin-Sensitive Site of Small-Conductance Calcium-Activated Potassium Channels.Molecules (Basel, Switzerland) · 2026Article
- Structural mechanisms for inhibition and activation of human small-conductance CaNature communications · 2026Article
- Mechanism of SK2 channel gating and its modulation by the bee toxin apamin and small molecules.eLife · 2025Article
- Investigating the immunomodulatory effects of honeybee venom peptide apamin inInfection and immunity · 2025Article
- Elimination of certain honeybee venom activities by adipokinetic hormone.Scientific reports · 2025Article
- Selectively Blocking Small Conductance CaBiology · 2025Article
- Dysfunction of Small-Conductance CaCells · 2024Article
- A single coiled-coil domain mutation in hIKCa channel subunits disrupts preferential formation of heteromeric hSK1:hIKCa channels.The European journal of neuroscience · 2024Article
- From Atrial Small-conductance Calcium-activated Potassium Channels to New Antiarrhythmics.European cardiology · 2024Review
- KJournal of neuroscience research · 2023Review
- Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells.Membranes · 2023Article
- Gating kinetics and pharmacological properties of small-conductance CaBiophysical journal · 2023Article
- TRPM7 restrains plasmin activity and promotes transforming growth factor-β1 signaling in primary human lung fibroblasts.Archives of toxicology · 2022Article
- Article
- Subtype-Selective Positive Modulation of KACS chemical biology · 2022Article
- The Inhibition of the Small-Conductance CaPharmaceuticals (Basel, Switzerland) · 2022Article
- Apamin structure and pharmacology revisited.Frontiers in pharmacology · 2022Article
- SK Channels Modulation Accelerates Equilibrium Recovery in Unilateral Vestibular Neurectomized Rats.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Differential regulation of KPhysiological reports · 2021Article
- Differential modulation of SK channel subtypes by phosphorylation.Cell calcium · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of small conductance calcium-activated potassium (K(Ca)2) channels can regulate neuronal firing and synaptic plasticity. They are characterized by their high sensitivity to the bee venom toxin apamin, but the mechanism of block is not understood. For example, apamin binds to both K(Ca)2.2 and K(Ca)2.3 with the same high affinity (K(D) approximately 5 pM for both subtypes) but requires significantly higher concentrations to block functional current (IC(50) values of approximately 100 pM and approximately 5 nM, respectively). This suggests that steps beyond binding are needed for channel block to occur. We have combined patch clamp and binding experiments on cell lines with molecular modeling and mutagenesis to gain more insight into the mechanism of action of the toxin. An outer pore histidine residue common to both subtypes was found to be critical for both binding and block by the toxin but not for block by tetraethylammonium (TEA) ions. These data indicated that apamin blocks K(Ca)2 channels by binding to a site distinct from that used by TEA, supported by a finding that the onset of block by apamin was not affected by the presence of TEA. Structural modeling of ligand-channel interaction indicated that TEA binds deep within the channel pore, which contrasted with apamin being modeled to interact with the channel outer pore by utilizing the outer pore histidine residue. This multidisciplinary approach suggested that apamin does not behave as a classical pore blocker but blocks using an allosteric mechanism that is consistent with observed differences between binding affinity and potency of block.
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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.