Gabriel, Tobias S. ; Hansen, Ulf-Peter ; Urban, Martin ; Drexler, Nils ; Winterstein, Tobias ; Rauh, Oliver ; Thiel, Gerhard ; Kast, Stefan M. ; Schroeder, Indra (2023)
Asymmetric Interplay Between K⁺ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K⁺ Channel Blocker Release.
In: Frontiers in Physiology, 2021, 12
doi: 10.26083/tuprints-00019966
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Modulating the activity of ion channels by blockers yields information on both the mode of drug action and on the biophysics of ion transport. Here we investigate the interplay between ions in the selectivity filter (SF) of K⁺ channels and the release kinetics of the blocker tetrapropylammonium in the model channel KcvNTS. A quantitative expression calculates blocker release rate constants directly from voltage-dependent ion occupation probabilities in the SF. The latter are obtained by a kinetic model of single-channel currents recorded in the absence of the blocker. The resulting model contains only two adjustable parameters of ion-blocker interaction and holds for both symmetric and asymmetric ionic conditions. This data-derived model is corroborated by 3D reference interaction site model (3D RISM) calculations on several model systems, which show that the K⁺ occupation probability is unaffected by the blocker, a direct consequence of the strength of the ion-carbonyl attraction in the SF, independent of the specific protein background. Hence, KcvNTS channel blocker release kinetics can be reduced to a small number of system-specific parameters. The pore-independent asymmetric interplay between K⁺ and blocker ions potentially allows for generalizing these results to similar potassium channels.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2023 |
| Autor(en): | Gabriel, Tobias S. ; Hansen, Ulf-Peter ; Urban, Martin ; Drexler, Nils ; Winterstein, Tobias ; Rauh, Oliver ; Thiel, Gerhard ; Kast, Stefan M. ; Schroeder, Indra |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Asymmetric Interplay Between K⁺ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K⁺ Channel Blocker Release |
| Sprache: | Englisch |
| Publikationsjahr: | 5 Dezember 2023 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2021 |
| Ort der Erstveröffentlichung: | Lausanne |
| Verlag: | Frontiers Media S.A. |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Frontiers in Physiology |
| Jahrgang/Volume einer Zeitschrift: | 12 |
| Kollation: | 13 Seiten |
| DOI: | 10.26083/tuprints-00019966 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/19966 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Modulating the activity of ion channels by blockers yields information on both the mode of drug action and on the biophysics of ion transport. Here we investigate the interplay between ions in the selectivity filter (SF) of K⁺ channels and the release kinetics of the blocker tetrapropylammonium in the model channel KcvNTS. A quantitative expression calculates blocker release rate constants directly from voltage-dependent ion occupation probabilities in the SF. The latter are obtained by a kinetic model of single-channel currents recorded in the absence of the blocker. The resulting model contains only two adjustable parameters of ion-blocker interaction and holds for both symmetric and asymmetric ionic conditions. This data-derived model is corroborated by 3D reference interaction site model (3D RISM) calculations on several model systems, which show that the K⁺ occupation probability is unaffected by the blocker, a direct consequence of the strength of the ion-carbonyl attraction in the SF, independent of the specific protein background. Hence, KcvNTS channel blocker release kinetics can be reduced to a small number of system-specific parameters. The pore-independent asymmetric interplay between K⁺ and blocker ions potentially allows for generalizing these results to similar potassium channels. |
| Freie Schlagworte: | selectivity filter, ion binding, blocker kinetics, 3D RISM, extended beta distributions, viral potassium channels, carbonyl-ion interaction |
| ID-Nummer: | 737834 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-199666 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 530 Physik 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Plant Membrane Biophyscis (am 20.12.23 umbenannt in Biologie der Algen und Protozoen) |
| Hinterlegungsdatum: | 05 Dez 2023 13:47 |
| Letzte Änderung: | 06 Dez 2023 08:44 |
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| Suche nach Titel in: | TUfind oder in Google |
Verfügbare Versionen dieses Eintrags
- Asymmetric Interplay Between K⁺ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K⁺ Channel Blocker Release. (deposited 05 Dez 2023 13:47) [Gegenwärtig angezeigt]
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