2. Academic Validation
  3. Activation of hTREK-1 by polyunsaturated fatty acids involves direct interaction

Activation of hTREK-1 by polyunsaturated fatty acids involves direct interaction

  • Sci Rep. 2024 Jul 2;14(1):15244. doi: 10.1038/s41598-024-66192-w.
Emilie Bechard 1,  Elodie Arel 1,  Jamie Bride 1,  Julien Louradour 1,  Xavier Bussy 1,  Anis Elloumi 2,  Claire Vigor 2,  Pierre Soule 3,  Camille Oger 2,  Jean-Marie Galano 2,  Thierry Durand 2,  Jean-Yves Le Guennec 1,  Hamid Moha-Ou-Maati 4 5,  Marie Demion 6
Affiliations

Affiliations

  • 1 PhyMedExp, Université de Montpellier, Inserm U1046, UMR CNRS 9412, CHU Arnaud de Villeneuve, Bâtiment Craste de Paulet, 370 Avenue du Doyen Gaston Giraud, 34290, Montpellier Cedex 05, France.
  • 2 IBMM, Université de Montpellier, UMR CNRS 5247, ENSCM, Montpellier, France.
  • 3 NanoTemper Technologies GmbH, Munich, Germany.
  • 4 IGF, Université de Montpellier, UMR CNRS 5203, Inserm 1191, Montpellier, France.
  • 5 INM, Inserm U1298, Montpellier, France.
  • 6 PhyMedExp, Université de Montpellier, Inserm U1046, UMR CNRS 9412, CHU Arnaud de Villeneuve, Bâtiment Craste de Paulet, 370 Avenue du Doyen Gaston Giraud, 34290, Montpellier Cedex 05, France. marie.demion@inserm.fr.
PMID: 38956407 DOI: 10.1038/s41598-024-66192-w
Abstract

TREK-1 is a mechanosensitive channel activated by polyunsaturated fatty acids (PUFAs). Its activation is supposed to be linked to changes in membrane tension following PUFAs insertion. Here, we compared the effect of 11 fatty acids and ML402 on TREK-1 channel activation using the whole cell and the inside-out configurations of the patch-clamp technique. Firstly, TREK-1 activation by PUFAs is variable and related to the variable constitutive activity of TREK-1. We observed no correlation between TREK-1 activation and acyl chain length or number of double bonds suggesting that the bilayer-couple hypothesis cannot explain by itself the activation of TREK-1 by PUFAs. The membrane fluidity measurement is not modified by PUFAs at 10 µM. The spectral shift analysis in TREK-1-enriched microsomes indicates a KD,TREK1 at 44 µM of C22:6 n-3. PUFAs display the same activation and reversible kinetics than the direct activator ML402 and activate TREK-1 in both whole-cell and inside-out configurations of patch-clamp suggesting that the binding site of PUFAs is accessible from both sides of the membrane, as for ML402. Finally, we proposed a two steps mechanism: first, insertion into the membrane, with no fluidity or curvature modifications at 10 µM, and then interaction with TREK-1 channel to open it.

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