Volume-sensitive outwardly rectifying chloride channels are involved in oxidative stress-induced apoptosis of mesangial cells

Abstract

Volume-sensitive outwardly rectifying (VSOR) Cl − channels have been electrophysiologically identified in human and mouse mesangial cells, but the functional role of VSOR Cl − channels in mesangial cell apoptosis is not clear. The aim of the present study was to demonstrate the role of VSOR Cl − channels in oxidative stress-induced mesangial cell apoptosis. H 2O 2-induced Cl − currents showed phenotypic properties of VSOR Cl − channels, including outward rectification, voltage-dependent inactivation at more positive potentials, sensitivity to hyperosmolarity, and inhibition by VSOR Cl − channel blockers. Moreover, blockage of VSOR Cl − channels by DIDS (100 μM), NPPB (10 μM) or niflumic acid (10 μM) rescued mesangial cell apoptosis induced by H 2O 2. Treatment with 150 μM H 2O 2 for 2 h resulted in significant reduction of cell volume, in contrast, nuclear condensation and/or fragmentation were not observed and the caspase-3 activity was also not increased. The early-phase alterations in cell volume were markedly abolished by pretreatment with VSOR Cl − channel blockers. We conclude that VSOR Cl −channels are involved in H 2O 2-induced apoptosis in cultured mesangial cells and its mechanism is associated with apoptotic volume decrease processes.