Table 3.
Effects of GABAAR mutations in vitro.
| Receptor Mutation | Affected receptor functions |
|---|---|
| GABAAR α1 S270I TM2 substitution | Not potentiated by 200 mM ethanol* (Mihic et al., 1997; Ueno et al., 1999) |
| GABAAR α1β1 S265I TM2 substitution | Reduced potentiation by ethanol (Mihic et al., 1997; Ueno et al., 1999) |
| GABAAR α2 A291W TM3 substitution | Reduced potentiation by ethanol and spontaneously open state (Mihic et al., 1997; Ueno et al., 1999, 2001) |
| GABAAR α2 S265I β1 S265I TM2 substitution γ2L | Reduced potentiation by 200 mM ethanol (90% WT/15% MUT; Wafford et al., 1991; Wafford and Whiting, 1992; Mihic et al., 1997; Ueno et al., 1999) |
| GABAAR α2β1 S265I TM2 substitution γ2L | Reduced potentiation by 200 mM ethanol (90% WT/20% MUT; Wafford et al., 1991; Wafford and Whiting, 1992; Mihic et al., 1997; Ueno et al., 1999) |
| GABAAR α2β1 S270I TM2 substitution γ2L | Reduced potentiation by 200 mM ethanol (90% WT/34% MUT; Wafford et al., 1991; Wafford and Whiting, 1992; Mihic et al., 1997; Ueno et al., 1999) |
| GABAAR α6 R100Q SNP substitution | Increased ethanol response with βδ but not βγ2 co-expression (Hanchar et al., 2005), but no effect in other studies (Botta et al., 2007) |
| in BDZ binding site | |
| GABAAR GABAAR ρ1 GlyR TM2 to TM3 | Potentiated by 200 mM ethanol (88% WT/48% C6; Mihic et al., 1997; Ueno et al., 1999) |
| 45 residue substitution | |
| GlyR α1 GABAAR γ-loop-2 chimera | No effect on ethanol sensitivity and general receptor function (Perkins et al., 2009) |
| GlyR α1 GABAAR δ-loop-2 chimera | Increased ethanol sensitivity but no effect on general receptor function (Perkins et al., 2009) |
| GlyR α1 GABAAR δ-loop-2 A52 chimera | Highly increased ethanol sensitivity but no effect on general receptor function (Perkins et al., 2009) |
| GlyR α1 GABAAR δ-loop-2 A52E chimera | Reduced ethanol sensitivity (Perkins et al., 2009) |
| GABAAR γ2L S265I | Unchanged potentiation by ethanol (Wafford et al., 1991; Wafford and Whiting, 1992; Mihic et al., 1997; Ueno et al., 1999) |
| GABAAR γ2L S270I | Unchanged potentiation by ethanol (Wafford et al., 1991; Wafford and Whiting, 1992; Mihic et al., 1997; Ueno et al., 1999) |
| GABAAR γ2L TM2/3 loop phosphorylation site mutant | Effect of ethanol blocked (Wafford et al., 1991; Wafford and Whiting, 1992) |
| GABAAR TM2 cysteine residue mutant | Covalent binding of general anesthetics irreversibly increases apparent agonist affinity and prohibits subsequent further potentiation by ethanol (Mascia et al., 2000) |
*See also GABA hypersensitive and spontaneously open A2(S270I) mutant (Ueno et al., 2001).