title: The purified mechanosensitive channel TREK-1 is directly sensitive to membrane tension.
abstract: Mechanosensitive channels are detected in all cells and are speculated to play a key role in many functions including osmoregulation, growth, hearing, balance, and touch. In prokaryotic cells, a direct gating of mechanosensitive channels by membrane tension was clearly demonstrated because the purified channels could be functionally reconstituted in a lipid bilayer. No such evidence has been presented yet in the case of mechanosensitive channels from animal cells. TREK-1, a two-pore domain K(+) channel, was the first animal mechanosensitive channel identified at the molecular level. It is the target of a large variety of agents such as volatile anesthetics, neuroprotective agents, and antidepressants. We have produced the mouse TREK-1 in yeast, purified it, and reconstituted the protein in giant liposomes amenable to patch clamp recording. The protein exhibited the expected electrophysiological properties in terms of kinetics, selectivity, and pharmacology. Negative pressure (suction) applied through the pipette had no effect on the channel, but positive pressure could completely and reversibly close the channel. Our interpretation of these data is that the intrinsic tension in the lipid bilayer is sufficient to maximally activate the channel, which can be closed upon modification of the tension. These results indicate that TREK-1 is directly sensitive to membrane tension.
authors.affiliation: Institut de Biochimie et Biophysique Moléculaire et Cellulaire (IBBMC), Unité Mixte de Recherche (UMR) 8619, CNRS, Université Paris-Sud, 91405 Orsay.
authors.forename: Catherine
authors.initials: C
authors.lastname: Berrier
authors.affiliation: Institute of Biology and Technology Saclay (iBitec-S), UMR 8221 Commissariat à l'Energie Atomique (CEA), CNRS, Université Paris-Sud and CEA Saclay, 91191 Gif sur Yvette, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pozza
authors.affiliation: Institute of Biology and Technology Saclay (iBitec-S), UMR 8221 Commissariat à l'Energie Atomique (CEA), CNRS, Université Paris-Sud and CEA Saclay, 91191 Gif sur Yvette, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: de Lacroix de Lavalette
authors.affiliation: Institut de Biochimie et Biophysique Moléculaire et Cellulaire (IBBMC), Unité Mixte de Recherche (UMR) 8619, CNRS, Université Paris-Sud, 91405 Orsay.
authors.forename: Solenne
authors.initials: S
authors.lastname: Chardonnet
authors.affiliation: Institut de Biochimie et Biophysique Moléculaire et Cellulaire (IBBMC), Unité Mixte de Recherche (UMR) 8619, CNRS, Université Paris-Sud, 91405 Orsay.
authors.forename: Agnes
authors.initials: A
authors.lastname: Mesneau
authors.affiliation: Institute of Biology and Technology Saclay (iBitec-S), UMR 8221 Commissariat à l'Energie Atomique (CEA), CNRS, Université Paris-Sud and CEA Saclay, 91191 Gif sur Yvette, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Jaxel
authors.affiliation: Institute of Biology and Technology Saclay (iBitec-S), UMR 8221 Commissariat à l'Energie Atomique (CEA), CNRS, Université Paris-Sud and CEA Saclay, 91191 Gif sur Yvette, France.
authors.forename: Marc
authors.initials: M
authors.lastname: le Maire
authors.affiliation: Institut de Biochimie et Biophysique Moléculaire et Cellulaire (IBBMC), Unité Mixte de Recherche (UMR) 8619, CNRS, Université Paris-Sud, 91405 Orsay. Electronic address: alexandre.ghazi@u-psud.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ghazi
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011312:Pressure; D013500:Surface Tension
chemical_list: D008081:Liposomes; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1
keywords: Liposomes; Mechanotransduction; Membrane Bilayer; Patch Clamp; Potassium Channels
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