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.