The role of the T-type calcium channel in cell division of cultured glial tumor cells

Changes in intracellular calcium are involved in cell cycle progression. Voltage-dependent calcium channels (VDCCs) are possible routes for the inward movement of calcium into the cell. VDCCs are generally classified as high or low-voltage activated channels consisting of L- and T-types, respectively. A recent review suggests an important role for T-type calcium channels in cellular proliferation. The expression of T-type calcium channels has been reported in proliferating undifferentiated cells whereas, upon differentiation, the density of the channel decreases. Since resected glial tumor cells were observed to differentiate in culture, we used an immortalized human astrocytoma cell line (U87MG) as a model to study the T-type calcium channel. Some comparisons to the L-type calcium channel were also made. The T-type calcium channel may be important in mediating the increase in intracellular calcium involved in cell cycle progression observed in astrocytic tumors.; The first aim of my research is to test whether VDCCs are expressed in cultured astrocytoma cells and compare these results to resected glial tumors. The second aim is to determine the pharmacology of VDCCs in astrocytoma cells using known calcium channel antagonists. The third aim is to determine whether VDCCs are involved in cell cycle progression of astrocytoma cells. The fourth aim of my research is to test the effects of variation of VDCC expression on proliferation of astrocytoma cells.; Our results showed that U87MG astrocytoma cells express both T- and L-type calcium channel isoforms. In resected glial tumors, only the expression of the T-type calcium channel increased with the malignancy of the tumor. T-type calcium channel antagonists inhibited cell division at sub-micromolar concentrations, more potently than L-type channel antagonists. The T-type calcium channel also showed sensitivity to the cell cycle and was observed to downregulate in the G0/G1 (non-proliferating) phase of the cell cycle. Varying the expression of the T-type calcium channel had a direct effect on the rate of proliferation of the astrocytoma cells. In conclusion, the T-type calcium channel may be involved in the proliferation of some tumors.