Analysis of calcium channels roles in cancer cells proliferation

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The TRPV2 channel is expressed in various tissues including neurons, neuroendocrine cells, epithelial cells in the kidney and liver and blood cells such as macrophages. In the present study, we investigated the regulation of the TRPV2 channel in macrophages. When macrophages were cultured in a serum-free condition, immunoreactivity of TRPV2 was detected largely in cytoplasm. Addition of serum induced translocation of some of the TRPV2 to the plasma membrane. A chemotactic peptide fMLP further induced translocation of the TRPV2 to the plasma membrane. In accordance with this observation, fMLP increased the Cs current in macrophage, which was inhibited by ruthenium red and the transfection of the dominant-negative mutant of TRPV2. fMLP-induced translocation of the TRPV2 was blocked by PI 3-kinase inhibitors and pretreatment with pertussis toxin. When cytoplasmic calcium concentration ([Ca2+]c)was monitored by using fura-2, fMLP induced a rapid and sustained elevation of [Ca2+]c, the latter of which was abolished by removal of extracellular calcium. Addition of ruthenium red or transfection of the dominant-negative mutant of TRPV2 did not affect the initial rise in [Ca2+]c but attenuated the sustained phase of fMLP-induced elevation of [Ca2+]c. Finally, addition of ruthenium red or transfection of dominant-negative mutant of TRPV2 inhibited chemotaxis of macrophage induced by fMLP. These results indicate that fMLP induces translocation of TRPV2 by a PI 3-kinase-dependent mechanism and this translocation is important for sustained elevation of [Ca2+]c in macrophage.