Re-evaluation of the water exchange lifetime value across red blood cell membrane

The water exchange lifetime (tau(i)) through red blood cell (RBC) membranes can be measured by analyzing the water protons bi-exponential T-1 and T-2 curves when RBCs are suspended in a medium supplemented with paramagnetic species. Since the seminal papers published in the early '70s of the previous century, paramagnetic Mn2+ ions were used for doping the extracellular compartment in the RBCs suspension. The obtained tau(i) values fall in the range of 9.8-14 ms. Conversely, other physic-chemical measurements afforded longer tau(i) values. Herein, it is shown that the replacement of Mn2+ with the highly stable, hydrophilic Gd(III) complexes used as paramagnetic magnetic resonance imaging (MRI) contrast agents led to measure tau(i) values of 19.1 +/- 0.65 ms at 25 degrees C. The observed difference is ascribed to the occurrence of enhanced permeability of RBC membrane in the presence of Mn2+ ions. This view finds support from the observation that an analogous behavior was shown in the presence of other divalent cations, such Ca2+ and Zn2+ ions. A possible role of scramblase has been hypothesized. Finally, tau(i) has been measured in presence of alcohols to show that the herein proposed method can detect minor changes in RBC membranes' stiffness upon the incorporation of aliphatic alcohols. (C) 2015 Published by Elsevier B.V.