Sedation and anesthesia mediated
by distinct GABA(A) receptor isoforms

by
Reynolds DS, Rosahl TW, Cirone J, O'Meara GF,
Haythornthwaite A, Newman RJ, Myers J, Sur C,
Howell O, Rutter AR, Atack J, Macaulay AJ,
Hadingham KL, Hutson PH, Belelli D, Lambert JJ,
Dawson GR, McKernan R, Whiting PJ, Wafford KA.
Merck Sharp & Dohme Research Laboratories,
The Neuroscience Research Centre,
Harlow, Essex CM20 2QR, United Kingdom.
J Neurosci. 2003 Sep 17;23(24):8608-17


ABSTRACT

The specific mechanisms underlying general anesthesia are primarily unknown. The intravenous general anesthetic etomidate acts by potentiating GABA(A) receptors, with selectivity for beta2 and beta3 subunit-containing receptors determined by a single asparagine residue. We generated a genetically modified mouse containing an etomidate-insensitive beta2 subunit (beta2 N265S) to determine the role of beta2 and beta3 subunits in etomidate-induced anesthesia. Loss of pedal withdrawal reflex and burst suppression in the electroencephalogram were still observed in the mutant mouse, indicating that loss of consciousness can be mediated purely through beta3-containing receptors. The sedation produced by subanesthetic doses of etomidate and during recovery from anesthesia was present only in wild-type mice, indicating that the beta2 subunit mediates the sedative properties of anesthetics. These findings show that anesthesia and sedation are mediated by distinct GABA(A) receptor subtypes.
People
GABA(A)
Etomidate
Isoflurane
Thiopentone
Anaesthesia
Nitrous oxide
Anaesthesia (pdf)
Inhaled anaesthetics
Obstetric anaesthesia
Molecular mechanisms
Chloroform anaesthesia
Anaesthesia: mechanisms
Molecular and cellular mechanisms
The GABA(A) receptor and general anaesthesia
Anaesthetic effects on neurotransmitter uptake
The beta3 subunit of GABA(A) and etomidate anaesthesia



Refs
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general-anaesthesia.com
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