Gabriel, Tobias S. ; Hansen, Ulf-Peter ; Urban, Martin ; Drexler, Nils ; Winterstein, Tobias ; Rauh, Oliver ; Thiel, Gerhard ; Kast, Stefan M. ; Schroeder, Indra (2021)
Asymmetric Interplay Between K+ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K+ Channel Blocker Release.
In: Frontiers in physiology, 12
doi: 10.3389/fphys.2021.737834
Artikel, Bibliographie
Dies ist die neueste Version dieses Eintrags.
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 Kcv. 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, Kcv 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: | 2021 |
| 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: | Bibliographie |
| Titel: | Asymmetric Interplay Between K+ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K+ Channel Blocker Release |
| Sprache: | Englisch |
| Publikationsjahr: | Oktober 2021 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Frontiers in physiology |
| Jahrgang/Volume einer Zeitschrift: | 12 |
| DOI: | 10.3389/fphys.2021.737834 |
| Zugehörige Links: | |
| 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 Kcv. 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, Kcv 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. |
| ID-Nummer: | pmid:34777005 |
| Zusätzliche Informationen: | Artikel-ID 737834 |
| 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: | 23 Nov 2021 06:35 |
| Letzte Änderung: | 06 Dez 2023 08:45 |
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| Suche nach Titel in: | TUfind oder in Google |
Verfügbare Versionen dieses Eintrags
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Asymmetric Interplay Between K⁺ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K⁺ Channel Blocker Release. (deposited 05 Dez 2023 13:47)
- Asymmetric Interplay Between K+ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K+ Channel Blocker Release. (deposited 23 Nov 2021 06:35) [Gegenwärtig angezeigt]
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