TRESK (KCNK18) is the most recently identfied member of the tandem pore potassium channel (K2P) family, which represent the molecular basis of background potassium currents. Mouse TRESK mRNA is expressed in several epithelial and neuronal tissues including lung, liver, kidney, brain and spinal cord. As revealed by in situ hybridization and quantitative RT-PCR most prominent expression was found in dorsal root ganglion (DRG) neurons, where TRESK current constitutes a major component of the standing outward current (IKso). Whole-cell recordings from DRG neurons elicited an IKso with an amplitude of 1.20 0.12 nA (n=25) when depolarised from a holding potential of -70 mV to -25 mV. This outward current reversed at -85 11 mV as would be expected from the Nernst equation for a potassium selective current. External acidification from pH 7.4 to 6.0 reduced this current by 54% to 0.56 0.07 nA (n=25). To investigate this pH-sensitive current further we prepared DRG neurons from functional TRESK knockout mice with a defective TRESK gene generated by ENU-based mutagenesis (Ingenium Pharmaceuticals). In these neurons, the standing outward current recorded in the whole-cell configuration only amounted to 0.887 0.137 nA (n=11) and acidification to pH 6.0 reduced the current amplitude by 31% to 0.563 nA 0.047 (n=11). The prominent expression of TRESK transcripts together with the existence of a pH-sensitive current component suggest that TRESK channels form the major background potassium current in murine DRG neurons. TRESK is ubiquitously expressed throughout the range of small to large diameter neurons and not restricted to small neurons like TRPV1, the capsaicin receptor, which processes noxious stimuli upon activation by heat or capsaicin, the pungent ingredient in hot chili pepper. Besides capsaicin there are several other components of plants acting on members of the TRP family, e.g. the clove-derived flavor eugenol that activates TRPV3. As TRP channels and TRESK subunits are coexpressed in DRG neurons we addressed the question whether they share some pharmacological properties. Upon expression in HEK-293 cells application of 2 mM eugenol reduced TRESK current amplitude by 93.75.6% (n=7). In additon, cinnamaldehyde (3 mM) also reduced TRESK currents to the same extent (91.52.5%, n=6), whereas capsaicin had no effect on TRESK. In summary, TRESK substantially contributes to IKso in DRG neurons thereby dampening neuronal excitability when cells are depolarised. In addition, TRESK serves as molecular target for plant ingredients which, until now, have only been known to activate TRP currents.