The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and Emergence
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Systems Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnsys.2017.00058/full |
| _version_ | 1819072810229694464 |
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| author | Iris Speigel Iris Speigel Edyta K. Bichler Edyta K. Bichler Paul S. García Paul S. García |
| author_facet | Iris Speigel Iris Speigel Edyta K. Bichler Edyta K. Bichler Paul S. García Paul S. García |
| author_sort | Iris Speigel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T17:43:38Z |
| format | Article |
| id | doaj.art-865173b012964e4fa402be45ee20e689 |
| institution | Directory Open Access Journal |
| issn | 1662-5137 |
| language | English |
| last_indexed | 2024-12-21T17:43:38Z |
| publishDate | 2017-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Neuroscience |
| spelling | doaj.art-865173b012964e4fa402be45ee20e6892022-12-21T18:55:33ZengFrontiers Media S.A.Frontiers in Systems Neuroscience1662-51372017-08-011110.3389/fnsys.2017.00058256122The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and EmergenceIris Speigel0Iris Speigel1Edyta K. Bichler2Edyta K. Bichler3Paul S. García4Paul S. García5Department of Anesthesiology, Emory University School of Medicine, AtlantaGA, United StatesResearch Division, Atlanta Veteran’s Affairs Medical Center, AtlantaGA, United StatesDepartment of Anesthesiology, Emory University School of Medicine, AtlantaGA, United StatesResearch Division, Atlanta Veteran’s Affairs Medical Center, AtlantaGA, United StatesDepartment of Anesthesiology, Emory University School of Medicine, AtlantaGA, United StatesResearch Division, Atlanta Veteran’s Affairs Medical Center, AtlantaGA, United StatesAnesthetics 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.http://journal.frontiersin.org/article/10.3389/fnsys.2017.00058/fullGABAreceptor traffickingsurface expressionextra-synaptic receptorstonic inhibitionanesthesia |
| spellingShingle | Iris Speigel Iris Speigel Edyta K. Bichler Edyta K. Bichler Paul S. García Paul S. García The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and Emergence Frontiers in Systems Neuroscience GABA receptor trafficking surface expression extra-synaptic receptors tonic inhibition anesthesia |
| title | The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and Emergence |
| title_full | The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and Emergence |
| title_fullStr | The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and Emergence |
| title_full_unstemmed | The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and Emergence |
| title_short | The Influence of Regional Distribution and Pharmacologic Specificity of GABAAR Subtype Expression on Anesthesia and Emergence |
| title_sort | influence of regional distribution and pharmacologic specificity of gabaar subtype expression on anesthesia and emergence |
| topic | GABA receptor trafficking surface expression extra-synaptic receptors tonic inhibition anesthesia |
| url | http://journal.frontiersin.org/article/10.3389/fnsys.2017.00058/full |
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