NCREASING OF THE FLUIDITY OF MODEL LIPID MEMBRANES UNDER THE INFLUENCE OF LOCAL ANESTHETICS

We have studied the effect of local anesthetics on the permeability of phospholipid liposomes of various composition to calcein. We have tested amides (lidocaine, prilocaine, mepivacaine and bupivacaine) and ester anesthetics (benzocaine, procaine and tetracaine). The permeability of large unilamellar liposomes to calcein has been determined by measuring the relative fluorescence intensity of calcein released from the phospholipid vesicles. We have shown that all tested amide anesthetics have little of feet on the leakage of calcein from dioleoylphosphocholine (DOPC) liposomes. The most effective amide was did bupivacaine. Substitution in the membranes of 20 mol % DOPC on tetraoleoylcardiolipin (TOCL) was did accompanied by increased activity of amides. Benzocaine and procaine at concentration up to 100 mM practically did not change DOPC liposome permeability. Addition of tetracaine up to concentration of 2 mM did not affect the permeability of vesicl. Further increas in the anesthetic concentration up to 50 mM led to increase in the intensity of calcein fluorescence and, at a concentration of 100 mM, a complete engagement of fluorescent marker was observed. In the case of vesicles including 20 mol % TOCL, the threshold concentration of tetracaine and the concentration that corresponded to 100% leakage of calcein were been 7 and 20 mM, respectively. Using confocal fluorescence microscopy of giant unilamellar vesicles formed from an equimolar mixture of DOPC and tetramyristoylcardiolipin (TMCL), we have shown that anesthetics destroy solid ordered domains, and this ability increases in the order: procaine d mepivacaine < bupivacaine n tetracaine. The revealed differences in the effect of local anesthetics might be caused by different depth of immersion of the anesthetics into the membrane.