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2020 - Possible Mechanisms of Toxicity of Local Aminoamide Anesthetics: Lipid-Mediated Action of Ropivacaine

icon vpp   Vesicle Prep Pro publication in Cell and Tissue Biology (2020)

Authors:
Zakharova A. A., Efimova S.S., Koryachkin V.A., Zabolotskii D.V., Ostroumova O.S. 

Journal:
Cell and Tissue Biolog (2020) 14, 218–227 doi: 10.1134/S1990519X20030098


Abstract:

This work is devoted to the identification of molecular mechanisms of action of local anesthetic ropivacaine and other aminoamides (mepivacaine and bupivacaine) on the membrane physicochemical properties and formation and functioning of various ion channels in model lipid bilayers. The boundary membrane potential and its components, permeability for fluorescent markers, and the temperature and cooperativity of the melting of membrane lipid, as well as the mosaic organization of the bilayer, were studied. It was found that ropivacaine, as well as mepivacaine and bupivacaine, changed the surface charge of the bilayer and increased the membrane boundary potential. It was demonstrated that the permeability of lipid vesicles for calcein increased with the introduction of aminoamides, while the temperature and cooperativity of the melting of saturated phosphocholines decreased. The effect of anesthetics on the packing density of lipids in the membrane correlated with the hydrophobicity of their molecules. A comparison of the effects of aminoamides allowed three mechanisms of anesthetics action on the functioning of ion channels to be determined: increasing the surface potential of the membrane, decreasing the packing density of lipids in the membrane, and blocking ion channels.


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