ArticleProceedings of the National Academy of Sciences of the United States of America2011
Crucial role of a shared extracellular loop in apamin sensitivity and maintenance of pore shape of small-conductance calcium-activated potassium (SK) channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 71 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
- Dysregulated cortical excitability and tau phosphorylation in a β3 integrin mouse model of autism.Brain : a journal of neurology · 2025Article
- Cryo-EM structures of the small-conductance CaNature communications · 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
- 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
- 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 modulation of SK channel subtypes by phosphorylation.Cell calcium · 2021Article
- Peptide Toxins Targeting KV Channels.Handbook of experimental pharmacology · 2021Review
- Inhibition of Small-Conductance, CaFrontiers in pharmacology · 2021Article
- Small Conductance CaFrontiers in physiology · 2021Article
- Effects of calcium-activated potassium channel modulators on afterhyperpolarizing potentials in identified motor and mechanosensory neurons of the medicinal leech.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2021Article
- Critical Role of E1623 Residue in S3-S4 Loop of Nav1.1 Channel and Correlation Between Nature of Substitution and Functional Alteration.Frontiers in molecular neuroscience · 2021Article
- Role of apamin-sensitive small conductance calcium-activated potassium currents in long-term cardiac memory in rabbits.Heart rhythm · 2018Article
- Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges.Frontiers in physiology · 2018Review
- Structural insights into the potency of SK channel positive modulators.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of small-conductance calcium (Ca(2+))-dependent potassium (K(Ca)2) channels (herein called "SK") produces membrane hyperpolarization to regulate membrane excitability. Three subtypes (SK1-3) have been cloned and are distributed throughout the nervous system, smooth muscle, and heart. It is difficult to discern the physiological role of individual channel subtypes as most blockers or enhancers do not discriminate between subtypes. The archetypical blocker apamin displays some selectivity between SK channel subtypes, with SK2 being the most sensitive, followed by SK3 and then SK1. Sensitivity of SK1 is species specific, with the human isoform being blocked by the toxin, whereas the rat is not. Mutation studies have identified residues within the outer pore that suggest apamin blocks by an allosteric mechanism. Apamin also uses a residue within the S3-S4 extracellular loop to produce a high-sensitivity block. We have identified that a 3-amino acid motif within this loop regulates the shape of the channel pore. This motif is required for binding and block by apamin, suggesting that a change in pore shape underlies allosteric block. This motif is absent in rat SK1, explaining why it is insensitive to block by apamin. The overlapping distribution of SK channel subtype expression suggests that native heteromeric channels may be common. We show that the S3-S4 loop of one subunit overlaps the outer pore of the adjacent subunit, with apamin interacting with both regions. This arrangement provides a unique binding site for each combination of SK subunits within a coassembled channel that may be targeted to produce blockers specific for heteromeric SK channels.
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