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Continuing Education in Anaesthesia, Critical Care & Pain Advance Access originally published online on January 3, 2006
Continuing Education in Anaesthesia, Critical Care & Pain 2006 6(2):49-53; doi:10.1093/bjaceaccp/mki068
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Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 2 2006 © The Board of Management and Trustees of the British Journal of Anaesthesia [2006]. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The molecular mechanisms of general anaesthesia: dissecting the GABAA receptor

Cameron J Weir, BSc(Hons) FRCA PhD
Consultant Anaesthetist/Senior Lecturer, Department of Anaesthesia, Ninewells Hospital and Medical School Dundee, DD1 9SY, Scotland, UK E-mail: c.j.weir@dundee.ac.uk
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Key points

Early theories of general anaesthetic action focused on nonspecific disruption of neuronal cell membranes.

Compelling evidence now demonstrates that certain general anaesthetics act in a highly specific manner upon central nervous system proteins.

Key amino acids within the {alpha} subunit of GABAA receptors may contribute to an anaesthetic binding pocket for volatile anaesthetic agents.

Genetically engineered mice harbouring single amino acid mutations at critical sites within GABAA receptor subunits lack certain components of i.v. anaesthetic activity in vivo.

GABAA receptors containing specific subunits appear to mediate the sedative (ß2 subtype) and anaesthetic (ß3 subtype) activity of i.v. anaesthetics.

 

The mechanisms underlying the dramatic clinical effects of general anaesthetics remain elusive. This review summarizes the remarkable developments which have occurred in general anaesthetic research over the past decade demonstrating that, rather than acting nonspecifically to disrupt lipid membranes, general anaesthetics target certain CNS proteins in a highly selective manner.


   Lipid theory of narcosis
 
. . . [Full Text of this Article]


   Anomalies with unitary theories
 

   Transmitter-gated ion channels
 

   GABA-gated receptors
 
Subunit composition and topology

Pharmacology of GABAA receptors


   In vitro studies
 
Single amino acids determine i.v. anaesthetic activity

A binding site for volatile anaesthetics?

In vivo studies

The role of the ß subunit in anaesthesia


   Anaesthetic targets
 

   Conclusions
 

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