Lipid mediators such as arachidonic acid and lysophosphatidylcholine (LPC) are implicated in the pathology of vascular diseases including atherosclerosis (Cox & Cohen, 1996). Ion channels are potential targets because several including the twin-pore potassium channels TREK-1 and TRAAK, and TRP channels are activated by lipid messengers. We screened for expression of the gene families encoding twin-pore potassium and TRP channels. RNA was isolated from fresh samples of mouse aorta and the smooth muscle layer of human saphenous vein (obtained with ethical approval) and specific RNA species detected by RT-PCR. Mice were killed humanely according to schedule 1 procedure. RNA encoding TREK-1, TRAAK, TRPM2 and TRPC5 was detected. TREK-1, TRAAK and TRPM2 are activated by arachidonic acid (Maingret et al., 2000, Hara et al., 2002) and western blotting revealed expression of TREK-1, TRPM2 and TRPC5 protein in human saphenous vein and mouse aorta. To explore if there is functional expression we used whole cell patch-clamp recording from freshly isolated aortic smooth muscle cells. A powerful inhibitory effect of 0.01 mM arachidonic acid occurred on voltage-gated potassium current but although we could show activation of over-expressed TREK-1 by arachidonic acid we did not observe activation of such a current in smooth muscle cells. Arachidonic acid evoked a large non-selective cationic current, as did hydrogen peroxide, which could be attributed to function of TRPM2 in vascular smooth muscle. Calcium-imaging was used to test for lipid regulation of TRPC5 over-expressed in HEK293 cells. In these cells the calcium signal was not affected by arachidonic acid (n=110, 4 coverslips) but was increased by 10 µM LPC (∆R350/380 = 0.223 ± 0.0104, (s.e.) n=87 cells, 3 coverslips). The effect of LPC was resistant to atropine and pertussis toxin pretreatment. There was no effect of LPC in the absence of TRPC5 expression (n=65 cells, 3 coverslips). In conclusion, we have found that vascular smooth muscle cells express several ion channels that are sensitive to activation by lipid signaling molecules such as arachidonic acid and LPC.