Sensory receptors throughout the body, including those in the oral epithelium, produce sensation in response to stimulation. Merkel cells (MCs) in the oral mucosa constitute a distinct cell population localized at the border between the epidermis and the dermis, and are believed to form part of an MC-neurite complex with myelinated Aβ-neurons which acts as a mechano-electric transducer. Transient receptor potential (TRP) channels, which constitute a large and functionally versatile family of cation-permeable transmembrane proteins, are mainly considered to be polymodal cell sensors involved in various cellular functions, including thermo/mechano/osmo-sensitivity. In rat footpad, these channels were found to be sensitive to mechanical and osmotic stimulation. The localization and physiological role of TRP channels in oral mucosal MCs, however, remain to be clarified. We isolated quinacrine-positive single MCs from hamster oral mucosa to investigate the expression, localization, and activity of TRP channels by immunohistochemical analysis and measurement of intracellular free Ca2+ concentration ([Ca2+]i) using fura-2 fluorescence. Intense immunoreaction for cytokeratin 20 (CK20), which co-localized with quinacrine fluorescence, was observed in the acutely isolated MCs. Both CK20 and quinacrine are used as specific markers to identify MCs. Intense immunoreactions for TRP vanilloid subfamily members (TRPV)-1, TRPV2, and TRPV4, and TRP ankyrin subfamily member (TRPA)-1 and TRP melastatin subfamily member (TRPM)-8 were observed on quinacrine-positive MCs. Transient increases in [Ca2+]i were osmo-dependently observed by application of hypo-tonic solution (140 to 300 mOsm/L). These [Ca2+]i increases were inhibited by TRPV1, TRPV2, TRPV4, or TRPA1 channel antagonists, but not by TRPM8 channel antagonist. In the presence of extracellular Ca2+, TRPV1, TRPV2, TRPV4, or TRPA1 channel agonists induced an increase in [Ca2+]i in MCs, but not in the absence of extracellular Ca2+. The present results indicate that hypo-tonic solution-induced membrane stretch activates TRPV1, TRPV2, TRPV4, and TRPA1 channels, and suggest that these channels play a key role as molecular sensors in the sensory transduction process in either MCs or MC-neurite complexes.