Human alpha and beta subunits contribute to the EC50 for GABA at the GABAA receptor expressed in Xenopus oocytes

The GABAA receptor/ionophore complex (GABAAR) may be composed of at least alpha, beta, and gamma subunits. Alpha subunits can influence the concentration of GABA at which a half maximal current response is elicited (EC50). There are no data to suggest that beta subunits can also influence this pharmacological property of the GABAAR. We examined the influence of human derived beta and alpha subunits on the EC50 for GABA. Nine different subunit combinations were evaluated: alpha 1, alpha 2, alpha 3 in combination with beta 1 gamma 2, beta 2 gamma 2, and beta 3 gamma 2. cRNA coding for these subunit combinations was injected into Xenopus oocytes that were subsequently recorded from using the two electrode voltage-clamp technique. A two-way analysis of variance showed that both alpha and beta subunits interact to influence the EC50 of GABAARs. The EC50 for alpha 3 changed significantly with beta subunits. The EC50 for alpha 2 was significantly different in beta 3 compared to beta 1 and beta 2 subunits, while the EC50 for alpha 1 was not significantly different between beta subunits. These findings suggests that other pharmacological and physiological properties may also be determined by interactions between alpha and beta subunits.