Dibucaine-induced modification of sodium transport in toad skin and of model membrane structures

The interaction of the local anesthetic dibucaine with the isolated toad sk in and membrane models is described. The latter consisted of human erythroc ytes, isolated unsealed human erythrocyte membranes (IUM), large unilamella r vesicles (LUV) of dimyristoylphosphatidylcholine (DMPC) and phospholipid multilayers built-up of DMPC and di-myristoylphosphatidylethanolamine (DMPE ), representative of phospholipid classes located in the outer and inner mo nolayers of the human erythrocyte membrane, respectively. Results indicate a significant decrease in the potential difference (PD) and in the short-ci rcuit current (Ise) after the application of dibucaine in toad skin, which may be interpreted as reflecting inhibition of the active transport of ions . This finding might be explained on the basis of the results obtained from fluorescence spectroscopy and X-ray diffraction studies on membrane models . In fact, dibucaine induced structural perturbations in IUM, DMPC LUV and phospholipid multilayers. Scanning electron microscopy revealed that dibuca ine induced erythrocyte stomatocytosis. According to the bilayer couple hyp othesis an echinocytic type of shape change would have been expected given the preferential interaction of dibucaine with DMPC. Although it is still p remature to define the molecular mechanism of action of dibucaine, the expe rimental results confirm the important role played by the phospholipid bila yers in the association of the anesthetic with cell membranes.