Initial studies of newly cloned GABAA receptors in heterologous expression studies indicated that some combinations of α and β subunits can form functional receptors (Schofield et al. 1987; Ymer et al. 1989) albeit lacking some characteristics of native channels (Pritchett et al. 1989). We found that functional GABAA channels can be formed from α2 and β2 subunits alone, although the currents are smaller than those produced by all 3 subunits (Figure 1A). To test our hypothesis that changing the relative abundance of individual GABAA receptor subunits could alter functional responses, we modified the amounts of either the α2 or γ3 subunit, keeping the concentration of the β2 subunit constant. As previous recombinant GABAA receptor studies had utilized 1:1:1 ratios we initially compared the 1:1:1 ratio with three-fold increases in either α2 (3:1:1) or γ3 subunits (1:1:3). GABAA receptors formed from different ratios of subunits had different responses to GABA. Increasing the amount of α2 mRNA (3:1:1 ratio of α:β:γ) produced significantly greater GABA currents than a 1:1:1 ratio of subunits (Figure 1B). Increasing the amount of γ3 subunit mRNA (1:1:3 ratio) reduced the GABA currents compared to either the 1:1:1 or 3:1:1 ratio of subunits.
