Modulation of RBC volume distributions by oxidants (phenazine methosulfate and tert-butyl hydroperoxide): Role of Gardos channel activation

A study was made comparing the effects of two oxidants - phenazine methosulfate (50-1500 µM) + 10 mM ascorbate and t-butyl hydroperoxide (1-3 mM) - on the volume-related parameters of normal human red blood cells. Incubation with either oxidative system for 20-30 min resulted in red blood cell density and osmotic resistance distribution shifts. Treatment with the phenazine methosulfate + ascorbate system in the presence of Ca2+ led to cell shrinking, with the maximum effect being more than 20%. In contrast, under the same conditions, t-BHP caused cell swelling by up to 15%. Modification of the suspending medium (Ca2+ removing, clotrimazole addition, or enrichment with K+) modulated the redistribution effects, suggesting that they were mediated to some extent by Gardos channel activation. These findings are important for understanding how oxidants modulate RBC cation channels.