| First Author | Sandoz G | Year | 2006 |
| Journal | EMBO J | Volume | 25 |
| Issue | 24 | Pages | 5864-72 |
| PubMed ID | 17110924 | Mgi Jnum | J:119946 |
| Mgi Id | MGI:3703490 | Doi | 10.1038/sj.emboj.7601437 |
| Citation | Sandoz G, et al. (2006) AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K(+) channels into open leak channels. EMBO J 25(24):5864-72 |
| abstractText | 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. |
