LIDOCAINE ACTION AND CONFORMATIONAL-CHANGES IN CYTOSKELETAL PROTEIN NETWORK IN HUMAN RED-BLOOD-CELLS

The mechanism of action of lidocaine, which is commonly used clinicall y as a local anesthetic, was studied in human red blood cells. The inf lux of [C-14]lidocaine through the cell membrane induced reversible tr ansformation of human red blood cells from discocytes to stomatocytes. This change in shape depended on the lidocaine concentration and requ ired both ATP and carbonic anhydrase. The lidocaine-induced shape chan ge occurred as a result of spectrin aggregation, which altered the int racellular environment of the human red blood cells, mediated by carbo nic anhydrase and activation of vacuolar type H+-ATPase (V-ATPase). Li docaine controlled the influx of Na-22 into the human red blood cells in a concentration-dependent manner. When incubated in media containin g ethylamino)-1-methyl-butyl]amino-2-methoxyacridine (mepacrine), an i nhibitor of Na+ channels, human red blood cells changed shape from dis cocytes to stomatocytes and the intracellular pH decreased. This pheno menon was very similar to the shape change induced by lidocaine. These results suggest that the mode of action of lidocaine is related to a conformational change in the cytoskeletal protein network.