Drug-induced shape change in erythrocytes correlates with membrane potential change and is independent of glycocalyx charge.

The influence of the anionic drugs indomethacin, barbitone, salicylate and the cationic drugs chlorpromazine and tetracaine on the morphology of human erythrocytes suspended in solutions of different chloride concentration (thus altering cell membrane potential) and constant osmolality, has been examined. As expected, the anionic and cationic drugs produced echinocytes and stomatocytes respectively in 145 mM NaCl. The cationic drugs induced fewer stomatocytes in 60 mM chloride than in 145 mM chloride at 37 degrees. Tetracaine induced echinocytes in 60 mM chloride at 20 degrees. Indomethacin and barbitone produced echinocytes in 145 mM chloride and stomatocytes in 60 mM chloride. Salicylate no longer produced echinocytes when the chloride concentration was reduced. Cells exposed to salicylate in 60 mM chloride were less cupped than the control cells. We suggest that the distribution of the charged form of the drug across the membrane is in equilibrium with the distribution of chloride ions. Changes in the intracellular drug concentration when the extracellular chloride is varied could then account for the observed shape changes in a manner which is consistent with the bilayer couple hypothesis for drug-membrane interactions. Cell glycocalyx charge depletion did not affect the shape induced by either the cationic or anionic drugs. The result suggests that any sialic acid dependent electric potential at the bilayer surface is small compared to the cell's zeta potential.