Abstract
Cell shrinkage is a hallmark of apoptosis. We previously demonstrated that the apoptotic volume decrease, which represents an early-phase event of apoptosis, is induced by K+ and Cl− efflux. On the other hand, it is known that osmotic cell shrinkage directly leads to apoptotic death in cells that lack the ability of volume regulation, called regulatory volume increase (RVI). In HeLa cells that can exhibit RVI, however, strong hypertonic stimulation failed to induce cell death. Since we have recently showed that the hypertonicity-induced non-selective cation channel (HICC) plays an important role in the RVI process in HeLa cells, we used flufenamate, a HICC blocker, to induce persistent cell shrinkage. Hypertonicity-induced cell death and activation of caspase-3 was enhanced by flufenamate in a concentration-dependent manner. The concentration dependency was in good accord with that for HICC current inhibition. These results suggest that HeLa cells are sensitized by inhibition of HICC to shrinkage-induced apoptosis. [J Physiol Sci. 2006;56 Suppl:S114]
