Convergence of Multiple Stimuli to a Single Gate in TREK1 and TRAAK Potassium Channels
| Autor: | Ismail Ben Soussia, Chatelain C Franck, Florian Lesage, Frank S. Choveau, Sylvain Feliciangeli, Delphine Bichet |
|---|---|
| Přispěvatelé: | Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV]Life Sciences [q-bio] Allosteric regulation pore gating Gating RM1-950 two-pore domain potassium channels Inhibitory postsynaptic potential 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Extracellular Pharmacology (medical) 030304 developmental biology Original Research Pharmacology 0303 health sciences allostery Correction Potassium channel 3. Good health Membrane stretch chemistry Cytoplasm openers Biophysics [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Arachidonic acid Therapeutics. Pharmacology extracellular pH 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Pharmacology Frontiers in Pharmacology, Frontiers, 2021, 12, ⟨10.3389/fphar.2021.755826⟩ Frontiers in Pharmacology, Frontiers, 2021, 12, pp.755826. ⟨10.3389/fphar.2021.755826⟩ Frontiers in Pharmacology, Vol 12 (2021) |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2021.755826⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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