Abstract

We studied gamma-aminobutyric acid (GABA) gated whole-cell Cl- currents after rapid transmitter application (< 10 ms) to cells expressing structurally different recombinant GABAA receptors. A variety of recombinant receptors were transiently transfected in a human cell line with three cDNAs encoding for different molecular forms of alpha-, beta- and gamma-subunits of the GABAA receptors. The maximal current amplitude elicited by GABA on recombinant GABAA receptors was greater when the alpha-subunits were combined with beta 2 gamma 2-subunits than with beta 1 gamma 2-subunits, with the exception of receptors including the alpha 6-subunit. The maximal current amplitude elicited by GABA was greater when the beta-subunits were combined with gamma 2 alpha 1-subunits than with gamma 1 alpha 1 subunits, with the exception of receptors including the beta 3-subunit. Furthermore, receptors comprising the beta 3-subunit had a greater sensitivity to GABA than those including the beta 1-or beta 2-subunits. When the gamma-subunits were substituted in receptors including alpha- and beta-subunits, the greatest current amplitude elicited by GABA was obtained with the alpha 1 beta 2 gamma 2 combination, whereas the GABA potency was greater with alpha 1 beta 2 gamma 1 and alpha 1 beta 1 gamma 3 than with the alpha 1 beta 2 gamma 2 combination. In receptors including alpha 6 beta 2-subunits the rank order of GABA maximal current amplitude was gamma 1 > gamma 2 > delta subunits.