ArticleFunction (Oxford, England)2022
Weak Cation Selectivity in HCN Channels Results From K
Article in Function (Oxford, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- Selectivity Filter Dynamics Define Ion Conductance and Selectivity Differences in CNG and HCN Channels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Constitutive sodium permeability in aProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural determinants of ivabradine block of the open pore of HCN4.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural basis for hyperpolarization-dependent opening of human HCN1 channel.Nature communications · 2024Article
- Alkali metal cations modulate the geometry of different binding sites in HCN4 selectivity filter for permeation or block.The Journal of general physiology · 2023Article
- When Is a Potassium Channel Not a Potassium Channel?Function (Oxford, England) · 2022Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate the pacemaker current which plays an important role in the timing of various biological processes like the heart beat. We used umbrella sampling to explore the potential of mean force for the conduction of potassium and sodium through the open HCN4 pore. Our data explain distinct functional features like low unitary conductance and weak selectivity as a result of high energetic barriers inside the selectivity filter of this channel. They exceed the 3-5 kJ/mol threshold which is presumed as maximal barrier for diffusion-limited conductance. Furthermore, simulations provide a thermodynamic explanation for the weak cation selectivity of HCN channels that contain only two ion binding sites in the selectivity filter (SF). We find that sodium ions bind more strongly to the SF than potassium and are easier released by binding of potassium than of another sodium. Hence ion transport and selectivity in HCN channels is not determined by the same mechanism as in potassium-selective channels; it rather relies on sodium as a weak blocker that can only be released by potassium.
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Registered trials
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