Convergence of Multiple Stimuli to a Single Gate in TREK1 and TRAAK Potassium Channels.
| Autor: | Choveau FS; Université Côte D'Azur, INSERM, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, Valbonne, France., Ben Soussia I; Université Côte D'Azur, INSERM, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, Valbonne, France., Bichet D; Université Côte D'Azur, INSERM, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, Valbonne, France., Franck CC; Université Côte D'Azur, INSERM, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, Valbonne, France., Feliciangeli S; Université Côte D'Azur, INSERM, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, Valbonne, France., Lesage F; Université Côte D'Azur, INSERM, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, Valbonne, France. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in pharmacology [Front Pharmacol] 2021 Sep 30; Vol. 12, pp. 755826. Date of Electronic Publication: 2021 Sep 30 (Print Publication: 2021). |
| DOI: | 10.3389/fphar.2021.755826 |
| Abstrakt: | Inhibitory potassium channels of the TREK1/TRAAK family are integrators of multiple stimuli, including temperature, membrane stretch, polyunsaturated fatty acids and pH. How these signals affect the gating of these channels is the subject of intense research. We have previously identified a cytoplasmic domain, pCt, which plays a major role in controlling channel activity. Here, we use pharmacology to show that the effects of pCt, arachidonic acid, and extracellular pH converge to the same gate within the channel. Using a state-dependent inhibitor, fluoxetine, as well as natural and synthetic openers, we provide further evidence that the "up" and "down" conformations identified by crystallography do not correspond to open and closed states of these channels. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Choveau, Ben Soussia, Bichet, Franck, Feliciangeli and Lesage.) |
| Databáze: | MEDLINE |
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