Bauer, Daniel ; Wissmann, Jan ; Moroni, Anna ; Thiel, Gerhard ; Hamacher, Kay (2022)
Weak Cation Selectivity in HCN Channels Results From K+-Mediated Release of Na+ From Selectivity Filter Binding Sites.
In: Function (Oxford, England), 3 (3)
doi: 10.1093/function/zqac019
Artikel, Bibliographie
Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Bauer, Daniel ; Wissmann, Jan ; Moroni, Anna ; Thiel, Gerhard ; Hamacher, Kay |
| Art des Eintrags: | Bibliographie |
| Titel: | Weak Cation Selectivity in HCN Channels Results From K+-Mediated Release of Na+ From Selectivity Filter Binding Sites |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Function (Oxford, England) |
| Jahrgang/Volume einer Zeitschrift: | 3 |
| (Heft-)Nummer: | 3 |
| DOI: | 10.1093/function/zqac019 |
| Kurzbeschreibung (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. |
| ID-Nummer: | pmid:36156894 |
| Zusätzliche Informationen: | Artikel-ID: zqac019 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Plant Membrane Biophyscis (am 20.12.23 umbenannt in Biologie der Algen und Protozoen) 10 Fachbereich Biologie > Computational Biology and Simulation |
| Hinterlegungsdatum: | 10 Okt 2022 10:16 |
| Letzte Änderung: | 11 Okt 2022 06:04 |
| PPN: | 500247854 |
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