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  Different Actions of General Anesthetics on the Firing Patterns of Neocortical Neurons Mediated by the GABAA Receptor

Antkowiak, B. (1999). Different Actions of General Anesthetics on the Firing Patterns of Neocortical Neurons Mediated by the GABAA Receptor. Anesthesiology, 91(2), 500-511. doi:10.1097/00000542-199908000-00025.

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Antkowiak, B1, 2, Author           
Affiliations:
1Former Department Comparative Neurobiology, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497800              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: BACKGROUND:

In cultured slice preparations of rat neocortical tissue, clinically relevant concentrations of volatile anesthetics mainly decreased action potential firing of neurons by enhancing gamma-aminobutyric acid (GABA(A)) receptor-mediated synaptic inhibition. The author's aim was to determine if other anesthetic agents are similarly effective in this model system and act via the same molecular mechanism.
METHODS:

The actions of various general anesthetics on the firing patterns of neocortical neurons were investigated by extracellular single-unit recordings.
RESULTS:

Pentobarbital, propofol, ketamine, and ethanol inhibited spontaneous action potential firing in a concentration-dependent manner. The estimated median effective concentration (EC50) values were close to or below the EC50 values for general anesthesia. Bath application of the GABA(A) antagonist bicuculline (100 microM) decreased the effectiveness of propofol, ethanol, halothane, isoflurane, enflurane, and diazepam by more than 90%, indicating that these agents acted predominantly via the GABA(A) receptor. The depressant effects of pentobarbital and ketamine were not significantly reduced by bicuculline treatment. Drugs acting mainly via the GABA(A) receptor altered the firing patterns of neocortical cells in different manners. Diazepam reduced the discharge rates by decreasing the number of action potentials per burst, leaving the burst rate unaffected. In contrast, muscimol, GABA, propofol, and volatile anesthetics decreased the burst rate.
CONCLUSIONS:

Although several anesthetic agents acted nearly exclusively via the GABA(A) receptor, they changed the discharge patterns of cortical neurons in different ways. This finding is explained by GABA-mimetic or benzodiazepine-like molecular interactions.

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 Dates: 1999-08
 Publication Status: Issued
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 Identifiers: DOI: 10.1097/00000542-199908000-00025
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Title: Anesthesiology
Source Genre: Journal
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Publ. Info: Philadelphia, Pa. [etc. : American Society of Anesthesiologists, etc.]
Pages: - Volume / Issue: 91 (2) Sequence Number: - Start / End Page: 500 - 511 Identifier: ISSN: 0003-3022
CoNE: https://pure.mpg.de/cone/journals/resource/954925379957