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.