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Related Experiment Videos

Gamma-aminobutyric acidA receptor function is inhibited by microtubule depolymerization

V J Whatley1, S J Mihic, A M Allan

  • 1Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.

The Journal of Biological Chemistry
|July 29, 1994
PubMed
Summary

Microtubules influence gamma-aminobutyric acidA (GABA_A) receptor function. Microtubule-disrupting agents inhibit GABA_A receptor activity, suggesting microtubules anchor these receptors at postsynaptic membranes.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Pharmacology

Background:

  • Microtubules are found at postsynaptic densities in the brain.
  • They are hypothesized to anchor neurotransmitter receptor clusters.
  • The specific role of microtubules in regulating gamma-aminobutyric acidA (GABA_A) receptor function remains uninvestigated.

Purpose of the Study:

  • To investigate the influence of microtubules on GABA_A receptor function.
  • To determine if microtubule-affecting agents alter GABA_A receptor activity.

Main Methods:

  • Assessed GABA_A receptor function by measuring muscimol-stimulated chloride uptake in cerebral cortical microsacs and proteoliposomes.
  • Measured GABA-mediated currents in Xenopus laevis oocytes expressing GABA_A receptors.

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  • Utilized microtubule-affecting agents like colchicine, nocodazole, vinblastine, and taxol.

    • Main Results:

    • Colchicine, nocodazole, vinblastine, and taxol inhibited muscimol-stimulated chloride uptake.
    • Colchicine reduced the potency of muscimol without altering ligand binding to the GABA_A receptor.
    • Purified GABA_A receptors in proteoliposomes, lacking microtubule components, were unaffected by colchicine.
    • Colchicine decreased protein kinase A activity in cortical microsacs.

    Conclusions:

    • Microtubule-depolymerizing agents inhibit GABA_A ergic function.
    • This inhibition is likely due to the disruption of interactions between GABA_A receptors and microtubules.
    • Protein kinase A modulation is not the mechanism behind colchicine's effect on GABA_A receptors.