Volume-activated chloride channels contribute to cell-cycle-dependent regulation of HeLa cell migration

The activation of volume-activated chloride Cl(-) channels has been implicated to play important roles in modulating cell cycle and cell migration. The aim of this study was to determine whether volume-activated Cl(-) channels are involved in cell-cycle-dependent regulation of cell migration in HeLa cells. Using techniques including cell-cycle synchronization, transwell migration assays and the patch-clamp technique, we demonstrate in this study that both the expression of volume-activated chloride current (I(Cl,vol)) and the potential of cell migration are cell-cycle-dependent; specifically, these events were high in G(0)/G(1) phase, low in S phase, and medium in G(2)/M phase. Moreover, the mean density of I(Cl,vol) was positively correlated to the rate of cell migration during cell-cycle progression. Additionally, endogenous suppression of I(Cl,vol) by transfecting cells with ClC-3 antisense oligonucleotides arrested cells in S phase and slowed cell migration. Collectively, our results suggest that volume-activated Cl(-) channels contribute to the cell-cycle-dependent regulation of cell migration.