In vascular smooth muscle, TRPC proteins are considered important components of store- and receptor-operated calcium channels (Beech, 2005; Albert et al., 2007). Among other TRP subfamilies, TRPM8 and TRPV4 appear the two predominant vascular subtypes (Inoue et al., 2006, Yang et al., 2006). The menthol receptor TRPM8 is the principal sensor of cold in primary sensory neurones (Bautista et al., 2007). In pulmonary arterial and aortic smooth muscle TRPM8 activation causes Ca²⁺ influx (Yang et al., 2006) but the whole range of vascular TRPM8 expression pattern and functions remain unknown. Vascular tissue was obtained from humanely-dispatched Wistar rats (12 weeks). Relative expression of TRPM8 was examined using RT-PCR, with GAPDH as endogenous control. TRPM8 mRNA was expressed in all tissues examined: brain, liver, tail artery, aorta and mesenteric artery. However, it was most abundantly expressed in aorta and mesenteric artery. Staining of cryostat sections of rat tail artery with TRPM8 rabbit antibody revealed TRPM8 immunoreactivity in smooth muscle cells, predominantly localised to cytoplasm. Confocal calcium (Fluo-4) imaging showed that 70% of tail artery myocytes (10 out of 14) responded to menthol (300 µM) with an intracellular Ca²⁺ rise and contraction (also Borisova et al. at this meeting). Furthermore, in voltage-clamped myocytes, 100 µM menthol induced outwardly rectifying cation currents, while STOCs discharge was initially accelerated and then almost completely suppressed, suggesting that TRPM8 activation can cause Ca²⁺ store release and eventual depletion. In isometric contraction studies, both icilin (10, 50 μM) and menthol (100, 300, 500 μM) evoked dose-dependent contractions in pre-tensed sections of tail artery (17±2% for 500 μM menthol expressed relative to contraction evoked by 60 mM KCl: 0.79±0.06 g, mean±S.E.M., n=29 from 14 animals). We conclude that TRPM8 channels are widely expressed and functional in arterial smooth muscles. These novel vascular large-conductance Ca²⁺ permeable cation channels may be involved in the regulation of vascular tone.