We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K<sup>+</sup> channels into open leak channels.
- Authors
Sandoz, Guillaume; Thümmler, Susanne; Duprat, Fabrice; Feliciangeli, Sylvain; Vinh, Joëlle; Escoubas, Pierre; Guy, Nicolas; Lazdunski, Michel; Lesage, Florian
- Abstract
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 β2AR 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 β2AR) and TREK-1 dock simultaneously.
- Subjects
NEUROSCIENCES; ION channels; MEMBRANE proteins; PROTEOMICS; MOLECULAR biology; NEUROTRANSMITTERS
- Publication
EMBO Journal, 2006, Vol 25, Issue 24, p5864
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7601437