Co-activation of nonselective cation channels by store depletion and oxidative stress in monocytic U937 cells.

Two different types of nonselective cation currents in monocytic U937 cells were characterized with the aid of patch-clamp technique. When the cells were exposed to oxidative stress with 10 mM H2O2, a nonselective cation current (INS) can be elicited. This current was still observed when extracellular cations are Ca2+. The change in intracellular Cl- concentrations did not shift the reversal potential of this current. This current showed no any rectification, and was time- and voltage-independent at any potentials. The further addition of LaCl3 (100 microM) or dithiothreitol (10 microM) effectively suppressed this current. However, SK & F 96365 (100 microM) or nifedipine (10 microM) did not produce any effect on it significantly. On the other hand, depletion of Ca2+ stores by different maneuvers, such as the application of ATP, thapsigargin or A23187, or dialysis of the cells with inositol-1,4,5-trisphosphate activated another type of nonselective current which was identified as store-operated Ca(2+)-permeable current (ISOC). Unlike H2O2-induced INS, this current was observed to slowly inactivate when the voltage steps were hyperpolarized. Current-voltage relation of this current showed inward rectification. When the cell was challenged with both store depletion and H2O2, INS on the top of ISOC can be activated. These results suggest that different types of nonselective cation channels can be co-expressed in the same cell. Therefore, in U937 cells nonselective cation currents can be activated after the stimulation with oxidative stress, store depletion or both. The activation of these nonselective cation channels may affect intracellular Ca2+ homeostasis.