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Article

  • The EMBO Journal (2006) 25, 5864 - 5872
  • doi:10.1038/sj.emboj.7601437

Published online: 16 November 2006

AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K+ channels into open leak channels

Guillaume Sandoz1,a, Susanne Thümmler1,a, Fabrice Duprat1, Sylvain Feliciangeli1, Joëlle Vinh2, Pierre Escoubas1, Nicolas Guy1, Michel Lazdunski1 and Florian Lesage1

  1. Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR6097, Institut Paul Hamel, Valbonne, France
  2. ESPCI, 10 rue Vauquelin, Paris, France

Correspondence to:

Florian Lesage, Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR6097, Institut Paul Hamel, 660, route des lucioles, 06560 Valbonne, France. Tel.: +33 4 93 95 77 32; Fax: +33 4 93 95 77 32; E-mail: lesage@ipmc.cnrs.fr

aThese authors contributed equally to this work

Received 26 June 2006; Accepted 16 October 2006

TREK channels are unique among two-pore-domain K+ channels. They are activated by polyunsaturated fatty acids (PUFAs) including arachidonic acid (AA), phospholipids, mechanical stretch and intracellular acidification. They are inhibited by neurotransmitters and hormones. TREK-1 knockout mice have impaired PUFA-mediated neuroprotection to ischemia, reduced sensitivity to volatile anesthetics and altered perception of pain. Here, we show that the A-kinase-anchoring protein AKAP150 is a constituent of native TREK-1 channels. Its binding to a key regulatory domain of TREK-1 transforms low-activity outwardly rectifying currents into robust leak conductances insensitive to AA, stretch and acidification. Inhibition of the TREK-1/AKAP150 complex by Gs-coupled receptors such as serotonin 5HT4sR and noradrenaline beta2AR is as extensive as for TREK-1 alone, but is faster. Inhibition of TREK-1/AKAP150 by Gq-coupled receptors such as serotonin 5HT2bR and glutamate mGluR5 is much reduced when compared to TREK-1 alone. The association of AKAP150 with TREK channels integrates them into a postsynaptic scaffold where both G-protein-coupled membrane receptors (as demonstrated here for beta2AR) and TREK-1 dock simultaneously.

  • Keywords:

    • G-protein-coupled receptors,
    • ion channels,
    • proteomics,
    • scaffolding