Abstract
TREK-1 (KCNK2 or K(2P)2.1) is a mechanosensitive K(2P) channel that is opened by membrane stretch as well as cell swelling. Here, we demonstrate that membrane phospholipids, including PIP(2), control channel gating and transform TREK-1 into a leak K(+) conductance. A carboxy-terminal positively charged cluster is the phospholipid-sensing domain that interacts with the plasma membrane. This region also encompasses the proton sensor E306 that is required for activation of TREK-1 by cytosolic acidosis. Protonation of E306 drastically tightens channel-phospholipid interaction and leads to TREK-1 opening at atmospheric pressure. The TREK-1-phospholipid interaction is critical for channel mechano-, pH(i)- and voltage-dependent gating.
MeSH terms
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Amino Acid Sequence
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Animals
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Biosensing Techniques*
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Cell Membrane / metabolism
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Cells, Cultured
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Hydrogen-Ion Concentration
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Ion Channel Gating*
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Mice
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Molecular Sequence Data
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Neurons / cytology
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Neurons / metabolism
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Patch-Clamp Techniques
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Phosphatidylinositol 4,5-Diphosphate / metabolism*
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Potassium / metabolism
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Potassium Channel Blockers / metabolism
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Potassium Channels, Tandem Pore Domain / chemistry*
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Potassium Channels, Tandem Pore Domain / genetics
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Potassium Channels, Tandem Pore Domain / metabolism*
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Protein Structure, Tertiary
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Protons
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Stress, Mechanical
Substances
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Phosphatidylinositol 4,5-Diphosphate
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Potassium Channel Blockers
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Potassium Channels, Tandem Pore Domain
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Protons
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Recombinant Fusion Proteins
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potassium channel protein TREK-1
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Potassium