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Organized Cultures of Nerve Tissue: A Novel Model System for Studies of Lipid Protein Interaction on the Functional Level

  • Michael Giesing
Part of the NATO Advanced Science Institutes Series book series (NSSA, volume 71)

Abstract

Organized fragments of grey matter of cerebral cortex (CC) maintained in vitro during cell maturation in the explant culture assembly are presented as a novel tool for studies on the functional impact of membrane phospholipids (PL). PL have been found to affect two transport systems and one receptor system. The specificity of the PL effects has been examined by analyzing the kinetics of proteins that bind glycine — an irrelevant amino acid neurotransmitter in CC — and γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the tissue. The composition of membrane constituents has been changed either through introduction of exogenous PL into the lipid matrix of viable cells or through specific degradation of asymmetrically distributed components. The following findings that were made are discussed:
  1. 1)

    The glycine carrier is a transversal protein that is governed by phosphatidylcholine (PC) but not by phosphatidylethanolamine (PE) in a fatty acid specific fashion. PC binds the ligand as well as it affects the protein. The carrier does not undergo lateral motion between ordered and fluid lipid domains. On the whole the glycine carrier is a protein with relatively little functional relation to the compositional mosaicism of the plasma membrane.

     
  2. 2)

    The GABA carrier is a mobile protein that seems to be localized to a major extent in the outer leaflet. Asymmetrically distributed PL regulate the activity of the protein in a fatty acid specific manner. The carrier can be inhibited as well as stimulated.

     
  3. 3)

    The GABA receptor is not a lipoprotein in nature. PL affect the receptor activity either through a single transversal modulator protein or through two asymmetrically distributed modulator proteins. PL that are components of the outer leaflet such as phosphatidyl-N-dimethylethanolamine (PDE) activate the inhibitory capacity of the modulator leading to a state of desensitization of the receptor that is characterized by an increase in the strength of ligand binding. Cytoplasmic PL, among them mainly PE and phosphatidyl-N-monoethanolamine (PME), induce a stimulation of GABA receptor binding through activation of the inner part of the transversal modulator or of the cytoplasmic modulator, thus creating a state of super-sensitivity. Cholinergic excess stimulation of the network of cultured neurons by bath application of carbachol increases PDE formation via the methylation pathway. This is accompanied by desensitization of the GABA receptor. The state of desensitization should be terminated through PE. The findings illustrate the functional specificity of PL in nerve tissue. It seems to be essential that viable cells are used since results stemming from artificial membranes of membrane preparations are not always the same.

     

Keywords

Gaba Receptor Polar Head Outer Leaflet Viable Nerve Cell Gaba Transport 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Michael Giesing
    • 1
  1. 1.Nattermann Research LaboratoriesKöln 30GFR

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