CaAmong ion channels, the transient receptor potential (TRP) melastatin 6 and 7 channel is similarly permeable to both of the dominant divalent cations Ca 2+ and Mg 2+ .(4) TRP channels were first cloned from the Drosophila species (TRP and transient receptor potential-like protein) and constitute a superfamily of proteins that encode a diverse group of Ca 2+ -permeable nonselective cation channels.(5) The TRP family is divided into three subfamilies: classic, vanilloid (TRPV), and melastatin type (TRPM).(5) The eight TRPM family members differ significantly from other TRP channels in terms of domain structure, cation selectivity, and activation mechanisms.(5) By mediating cation entry as well as membrane depolarization, activation of the TRPM subfamily of ion channels has a profound influence on various physiologic and pathologic processes. (6,7) TRPM7 is endogenously expressed in a wide variety of tissues including brain and hematopoietic tissues (8) as well as kidney and heart tissues.(9-11) The TRPM7 cation channel supports multiple cellular and physiological functions, including cellular Mg 2+ homeostasis, (12,13) cell viability and growth, (13)(14)(15)(16) anoxic neuronal cell death, (17) synaptic transmission, (18) cell adhesion, (19,20) and intestinal pacemaking.(21) Recently, Wykes et al. (22) suggested that TRPM7 channels are critical for human mast cell survival, and Jiang et al. (23) suggested that activation of TRPM7 channels is critical for the growth and proliferation of human head and neck carcinoma cells. Also Abed et al. (24) proposed the importance of TRPM7 in human osteoblast-like cell proliferation. However, the presence and potential function of TRPM7 channels in human gastric cancer cells are unknown.In this study, we examined the presence and potential role of TRPM7 channels in the growth and survival of AGS cells, the most common human gastric adenocarcinoma cell line. Our data suggest that TRPM7 channels have an important role in the survival of these tumor cells. Materials and MethodsCells. Five human gastric adenocarcinoma cell lines (AGS, MKN-1, MKN-45, SNU-1, and SNU-484) were used. Among them, we used mainly AGS cell line, the most common human gastric adenocarcinoma cell line. All cell lines were established at

Background: Activation of TRPC4/5 channels is mediated by GPCR activation. Results: TRPC4/5 was activated by the G␣ i/o -coupled receptor and the G␣ i protein, which interacted directly with each other. Conclusion: G␣ i proteins play an essential role as novel activators of TRPC4/5. Significance: Our findings provide new insights into the activation mechanism of inhibitory G␣ proteins.

Menthol, a naturally occurring compound from peppermint oil, binds and activates the TRPM8 Ca(2+)-permeable channel that exhibits abnormal expression patterns in prostate cancer, suggesting that TRPM8 links Ca(2+) transport pathways to tumor biology. We thus investigated the cellular responses of prostate cancer cells to menthol. Here we found that menthol increases [Ca(2+)](i) via Ca(2+) influx mechanism(s) independent of TRPM8 in PC-3 cells. We demonstrated that menthol induces cell death at supramillimolar concentrations in PC-3 cells and the cell death is not suppressed by low extracellular Ca(2+) condition which indicates that menthol-induced cell death is not associated with Ca(2+) influx pathways. In addition, we showed that menthol increases a phosphorylated form of c-jun N-terminal kinase (JNK) in PC-3 cells through TRPM8-independent mechanisms. Thus, our data indicate that there is an apparent lack of causality between TRPM8 activation and menthol-induced cell death and that menthol can regulate TRPM8-independent Ca(2+)-transport and cellular processes.