CELL CYCLE-DEPENDENT EXPRESSION OF A GLIOMA-SPECIFIC CHLORIDE CURRENT- PROPOSED LINK TO CYTOSKELETAL CHANGES

We recently demonstrated expression of a novel, glioma-specific Cl- cu rrent in glial-derived tumor cells (gliomas), including stable cell li nes such as STTG1, derived from a human anaplastic astrocytoma. We use d STTG1 cells to study whether glioma Cl- channel (GCC) activity is re gulated during cell cycle progression. Cells were arrested in defined stages of cell cycle (G(0), G(1), G(1)/S, S, and M phases) using serum starvation, mevastatin, hydroxyurea, demecolcine, and cytosine beta-D -arabinofuranoside. Cell cycle arrest was confirmed by measuring [H-3] thymidine incorporation and by DNA flow cytometry. Using whole cell pa tch-clamp recordings, we demonstrate differential changes in GCC activ ity after cell proliferation and cell cycle progression was selectivel y altered; specifically, channel expression was low in serum-starved, G(0)-arrested cells, increased significantly in early G(1), decreased during S phase, and increased after arrest in M phase. Although the Li nk between the cell cycle and GCC activity is not yet clear, we specul ate that GCCs are Linked to the cytoskeleton and that cytoskeletal rea rrangements associated with cell division lead to the observed changes in channel activity. Consistent with this hypothesis, we demonstrate the activation of GCC by disruption of F-actin using cytochalasin D or osmotic cell swelling.