title: The neuronal lipid membrane permeability was markedly increased by bupivacaine and mildly affected by lidocaine and ropivacaine.
abstract: We investigated the local anesthetic action on ionic membrane conductance (membrane conductance) and selectivity in membranes formed with neuronal phospholipids in the absence and presence of cholesterol. In membranes without cholesterol, 1 mM bupivacaine and ropivacaine increased the membrane conductance approximately 4.5-fold; and 5 mM lidocaine, ropivacaine and bupivacaine increased the membrane conductance by 2.7-, 2.8- and 22.2-fold, respectively. In the presence of cholesterol, 5 mM ropivacaine had no effect, lidocaine decreased the membrane conductance by 2-fold, and bupivacaine increased the membrane conductance by 17-fold. Local anesthetics did not affect the ion selectivity in membranes without cholesterol, but they all decreased the Na(+) selectivity in membranes with cholesterol. Cholesterol reduced the lidocaine- and ropivacaine-induced membrane conductance increase by eliminating or reversing the Na(+) conductance increase and by lowering the Cl(-) conductance increase. In the absence of cholesterol, 5 mM bupivacaine increased both Na(+) conductance (38-fold) and Cl(-) conductance (19-fold), while in the presence of cholesterol it only increased Cl(-) conductance (26-fold). Of the local anesthetics studied, ropivacaine was the least membrane toxic while bupivacaine was the most toxic.
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Pardo
authors.forename: Thomas J J
authors.initials: TJ
authors.lastname: Blanck
authors.forename: Esperanza
authors.initials: E
authors.lastname: Recio-Pinto
mesh_terms: D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D051381:Rats; D000077212:Ropivacaine; D012964:Sodium / Q000378:metabolism
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D002712:Chlorides; D008563:Membrane Lipids; D000077212:Ropivacaine; D002784:Cholesterol; D008012:Lidocaine; D012964:Sodium; D002045:Bupivacaine