Cholesterol and Cardiolipin Importance in Local Anesthetics–Membrane Interactions: The Langmuir Monolayer Study View Full Text


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Article Info

DATE

2019-02

AUTHORS

Justyna Mildner, Anita Wnętrzak, Patrycja Dynarowicz-Latka

ABSTRACT

Local anesthetics (LAs) are known to act on membrane level; however, the molecular mechanism of their activity is still not fully understood. One hypothesis holds that these drugs can incorporate into lipid membrane of nerve cells and in this way change conformation of channel proteins responsible for transport of sodium ions. However, the action of anesthetics is not limited to nerve cells. These drugs also affect other types of cells and organelles, causing severe side effects. In this paper, we applied Langmuir monolayers-as model of cellular membranes-and investigated interactions between selected amide-type local anesthetics (lidocaine prilocaine, mepivacaine and ropivacaine, in the form of hydrochlorides) and lipid components of natural membranes: cholesterol, POPC and cardiolipin (CL) and their mixtures (POPC/cholesterol and POPC/CL/cholesterol), which can serve as simplified models of nerve cell membranes, erythrocytes, and mitochondria. The influence of the drug was monitored by registering the surface pressure (π) as a function of surface area per molecule (A) in a monolayer in the presence of the drug in the subphase. The structure of lipid monolayers on subphases containing and devoid of the studied drugs were visualized with Brewster angle microscopy (BAM). Langmuir monolayer studies complemented with surface visualization technique reveal the expansion and fluidization of lipid monolayers, with the most pronounced effect observed for cardiolipin. In mixed systems, the effect of LAs was found to depend on cholesterol proportion. The observed fluidization of membranes by local anesthetics may negatively affect cells functioning and therefore can explain side effects of these drugs both on the cardiovascular and nervous systems. More... »

PAGES

1-9

References to SciGraph publications

Journal

TITLE

The Journal of Membrane Biology

ISSUE

N/A

VOLUME

N/A

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00232-018-0055-6

    DOI

    http://dx.doi.org/10.1007/s00232-018-0055-6

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30506104


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