Allosteric modulation in spontaneously active mutant γ-aminobutyric acidA receptors in frogs
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Cited by (12)
Binding, activation and modulation of Cys-loop receptors
2010, Trends in Pharmacological Sciencesγ-aminobutyric acid type A (GABA <inf>A</inf> ) receptor subtype inverse agonists as therapeutic agents in cognition
2010, Methods in EnzymologyCitation Excerpt :The transitions between the various states (R, A, D) have different “energy barriers” and each state can be stabilized by ligand binding (Hogg et al., 2005). Certain types of receptors have been found to be constitutively active (CA or spontaneously active without ligand) and it is likely that, in this case, the open state is energetically relatively more stable (Findlay et al., 2000; Hogg et al., 2005). The existence of constitutive activity for G protein-coupled receptors (GPCRs) was first described by Costa (Costa and Herz, 1989) and is now firmly rooted in receptor pharmacology (Milligan, 2003).
GABA<inf>A</inf> receptors and alcohol
2008, Pharmacology Biochemistry and BehaviorTransmembrane residues define the action of isoflurane at the GABA <inf>A</inf> receptor alpha-3 subunit
2005, Brain ResearchCitation Excerpt :These receptors displayed ∼100-fold increase in sensitivity to GABA (EC50 = 0.22 μM, n = 12), while the Hill coefficient (nH = 1.17 ± 0.08) and maximal currents (IMAX = −634 ± 134 pA) were unchanged. Previous reports have demonstrated that mutation of specific residues within the TM domains of GABAA subunits associated with increased agonist potency produces spontaneously open channels [6,13]. To test this possibility in the α3 subunit, we applied 100 μM of the channel blocker picrotoxin (PTX) in the absence of GABA to HEK293 cells expressing wild-type and mutant α3 receptors.
The anesthetic-like effects of diverse compounds on wild-type and mutant γ-aminobutyric acid type A and glycine receptors
2008, Anesthesia and AnalgesiaCitation Excerpt :Both possibilities would, however, suggest that, in this case, the mutations we studied affected transduction of a nonspecific effect of SDS on interfacial properties. This is also consistent with mutation of amino acid 270 of the GABAA receptor to other residues, which have been shown to affect signal transduction which causes mutation of the serine in position 270 of the GABAA receptor to tryptophan affects channel gating, but also reduces the effect of other positive modulators.27 The prediction that GABA would positively modulate Gly receptor function, and that Gly would modulate GABAA receptor function, was based on a theory of anesthesia that proposes that anesthetics modulate bilayer properties that are coupled to receptor function.17