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Author Notes:

Correspondence: Paul S. García pgarcia@emory.edu

IS performed the literature search, organized the theme, wrote the first draft, and constructed the table. EB and PG added key concepts/references as well as co-wrote and co-edited the manuscript.

We acknowledge that part of this work appears in dissertation form (Speigel, 2017).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

This work was supported by the James S. McDonnell Foundation (award number 220020346, PG), the National Institute of Health (F31NS086370, IS) and the U.S. Department of Veterans Affairs (award number BX001677, PG).

Keywords:

  • GABA
  • POCD
  • anesthesia
  • extra-synaptic receptors
  • receptor trafficking
  • surface expression
  • tonic inhibition

The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and Emergence.

Tools:

Journal Title:

Frontiers in Systems Neuroscience

Volume:

Volume 11

Publisher:

, Pages 58-58

Type of Work:

Article | Final Publisher PDF

Abstract:

Anesthetics produce unconsciousness by modulating ion channels that control neuronal excitability. Research has shown that specific GABAA receptor (GABAAR) subtypes in particular regions of the central nervous system contribute to different hyperpolarizing conductances, and behaviorally to distinct components of the anesthetized state. The expression of these receptors on the neuron cell surface, and thus the strength of inhibitory neurotransmission, is dynamically regulated by intracellular trafficking mechanisms. Pharmacologic or activity-based perturbations to these regulatory systems have been implicated in pathology of several neurological conditions, and can alter the individual response to anesthesia. Furthermore, studies are beginning to uncover how anesthetic exposure itself elicits enduring changes in subcellular physiology, including the processes that regulate ion channel trafficking. Here, we review the mechanisms that determine GABAAR surface expression, and elaborate on influences germane to anesthesia and emergence. We address known trafficking differences between the intrasynaptic receptors that mediate phasic current and the extra-synaptic receptors mediating tonic current. We also describe neurophysiologic consequences and network-level abnormalities in brain function that result from receptor trafficking aberrations. We hypothesize that the relationship between commonly used anesthetic agents and GABAAR surface expression has direct consequences on mature functioning neural networks and by extension ultimately influence the outcome of patients that undergo general anesthesia. Rational design of new anesthetics, anesthetic techniques, EEG-based monitoring strategies, or emergence treatments will need to take these effects into consideration.

Copyright information:

© 2017 Speigel, Bichler and García.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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