Vascular function of the placenta is closely linked with the well being of the fetus. Key to this is the effective transport of blood and gases which is possible due to the low resistance of the placenta. There is a poor understanding about the specific ion channels that are involved in regulating the vessel tone across the placenta. Two members of the K2P family TWIK-2 and TREK-1 are important for maintaining the resting membrane potential. This study aims to investigate the expression of these ion channels in arteries taken from the human chorion and villi. Hypothesis: TWIK-2 and TREK-1 expression is differentially modulated across the fetal and maternal interface of the placenta. Placentae were collected with written informed consent from patients undergoing elective Caesarean section at term (≥37 weeks). Explants taken from the stem villous artery (SVA) and the third branch of the chorionic plate artery (CPA) were used to culture smooth muscle cells (SMC). After 20 days the cells were harvested and immunofluoresence was used to detect the expression of TWIK-2 and TREK-1. Briefly SMC were fixed with 3% PFA and pre incubated with primary antibody to detect expression of the K2P channels (Alomone, Jerusalem).Western blotting was performed on crude tissue lysate and separated by 12% SDS-PAGE to quantify expression of TWIK-2 and TREK-1 in CPA and SVA. The blots were stripped and re-probed with beta actin (AbCam, UK) to measure protein loading. Immunofluorescence for TWIK-2 and TREK-1 was detected in both CPA and SVA and staining for alpha actin confirmed the smooth muscle cell phenotype (n = 4 placentae). Staining was concentrated in the nuclei of SMC cultured from CPA, while in SVA, the staining was cytosolic and showed actin like stress fibres. Western blot analysis on isolated placental arteries showed that the TREK-1 dimer (100 kDa) band density is significantly higher in SVA (n =6 placentae; P= 0.04). No significant difference was seen with TWIK-2 (37 kDa) in the two different vessel types (n =6 placentae; P=0.47). We have successfully shown that TWIK-2 and TREK-1 are expressed in both the SVA and CPA. Our early findings suggest TREK-1 is up regulated in the SVA and the immunofluorescence staining shows the channel may be differentially regulated within the two vascular beds. These findings suggest that TWIK-2 and TREK-1 may have an important role in regulating vasodilatation of placental arteries and requires further investigation. This also raises the possibility that K2P channels are a potential target for treating placental disorders such as pre eclampsia where the vascular arteries are poorly perfused and do not respond well to vasodilators.