The specific mechanisms underlying general anesthesia are primarily unknown. The intravenous general anesthetic etomidate acts by potentiating GABAA receptors, with selectivity for 2 and 3 subunit-containing receptors determined by a single asparagine residue. We generated a genetically modified mouse containing an etomidate-insensitive 2 subunit (2 N265S) to determine the role of 2 and 3 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 3-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 2 subunit mediates the sedative properties of anesthetics. These findings show that anesthesia and sedation are mediated by distinct GABAA receptor subtypes.
|Number of pages||10|
|Journal||Journal of Neuroscience|
|Publication status||Published - Sep 2003|
- Anaesthetics pharmacology
- Etomidate pharmacology
- Hypnotics and sedatives pharmacology
- GABA-A metabolism