Mutant human alpha(1)beta(1)(T262Q) GABA(A) receptors are directly activated but not modulated by pentobarbital.
Pentobarbital activates GABA(A) receptors and enhances GABA-activated currents. A threonine residue (262) in the second membrane spanning region at the 12' position in the beta(1) subunit, alpha(1)beta(1)(T12'Q), is necessary for the potentiating action of pentobarbital. We examined whether T12'Q-mutated receptors expressed in Spodoptera frugipedra (Sf 9) cells responded to direct activation by pentobarbital. In both mutant and wild type receptors, pentobarbital (100 microM to 1 mM) evoked a current response. The pentobarbital EC(50) values were similar; 119 and 158 microM for alpha(1)beta(1) and alpha(1)beta(1)(T12'Q) receptors, respectively. The results show it is possible to discriminate between agonistic and potentiating effects of pentobarbital, suggesting these actions involve separate mechanisms.
Dalziel
J E
JE
Membrane Biology Program, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Cox
G B
GB
Gage
P W
PW
Birnir
B
B
D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009154:Mutation; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018757:GABA Modulators; D011963:Receptors, GABA-A; D011993:Recombinant Fusion Proteins; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital