Expression of functional receptors by the human gamma-aminobutyric acid A gamma 2 subunit.
gamma-Aminobutyric acid A (GABA(A)) receptors are heteromeric membrane proteins formed mainly by various combinations of alpha, beta, and gamma subunits; and it is commonly thought that the gamma 2 subunit alone does not form functional receptors. In contrast, we found that cDNA encoding the gamma 2L subunit of the human GABA(A) receptor, injected alone into Xenopus oocytes, expressed functional GABA receptors whose properties were investigated by using the two-microelectrode voltage-clamp technique. GABA elicited desensitizing membrane currents that recovered after a few minutes' wash. Repetitive applications of GABA induced a "run-up" of GABA currents that nearly doubled the amplitude of the first response. The GABA currents inverted direction at about -30 mV, indicating that they are carried mainly by Cl(-) ions. The homomeric gamma 2L receptors were also activated by beta-alanine > taurine > glycine, and, like some types of heteromeric GABA(A) receptors, the gamma 2L receptors were blocked by bicuculline and were potentiated by pentobarbital and flunitrazepam. These results indicate that the human gamma 2L subunit is capable of forming fully functional GABA receptors by itself in Xenopus oocytes and suggest that the roles proposed for the various subunits that make up the heteromeric GABA(A) receptors in situ require further clarification.
Laboratory of Cellular and Molecular Neurobiology, Department of Neurobiology and Behavior, University of California, McGaugh Hall 1115, Irvine, CA 92697-4550, USA. ataulfo@calli.cnb.unam.mx
Ataúlfo
A
Martínez-Torres
Ricardo
R
Miledi
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D005260:Female; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology; D010957:Plasmids; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology
D000596:Amino Acids; C546279:GABRG2 protein, human; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital