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The TREK channel belongs to the superfamily of two-pore-domain potassium channels (K2P-channels) that are made up of four transmembrane segments (TM1 - TM4) and two pore-forming domains that are arranged in tandem. The activity of these channels is directly regulated by the intracellular pH, heat, polyunsaturated fatty acids, phospholipids and mechanical stretch. Currently little is known about the pore structure and how these different stimuli gate the pore in structural terms. To this end we employed systematic cysteine scanning mutagenesis on the four TM domains and functionally characterised these mutants in several respects: I) using chemical cysteine modification we identified pore lining residues, II) by measuring detailed pH dose response curve we identified residues involved in the pH gating mechanism and III) by studying different pore blocking compounds we identified potential blocker interacting residues. These sets of functional data will be evaluated in the context of structural models of the TREK channel pore in the closed and open state.