Functional Characteristics of alpha3beta3gamma2 and alpha1beta2gamma2 GABA-A receptors

Abstract

The GABAA receptor is a member of the cys-loop family of ligand gated ion channels and the major mediator of neuronal inhibition. Each receptor is a pentameric protein complex composed of homologous subunits, the combination of which gives rise to numerous GABAA receptor subtypes. Within the thalamus, two synaptic GABAA receptor isoforms predominate; the α1β2γ2 channels, which are found at the synapses of relay neurons, and the α3β3γ2 channels that are located at synapses in the reticular nucleus. We endeavoured to characterize the kinetic properties to these two GABAA receptors. Our preliminary data suggest that both receptors open to a single channel conductance level of 26 pS, irrespective of the GABA concentration used to elicit activity. α3β3γ2 GABAA receptors, however, exhibit longer active periods (bursts) at saturating (5 mM) and low (2 μM) concentrations of GABA compared to α1β2γ2 GABAA receptors. The mean burst length and intra-burst open probability (Po) for the α3β3γ2 channels was 136.7 ± 16.8 ms and 0.84 ± 0.05 (n = 4), respectively and for the α1β2γ2 channels was 87.4 ± 12.0 ms and 0.82 ± 0.02 (n = 3), respectively, when exposed to 5 mM GABA. At 2 μM GABA, the mean burst length and Po for α3β3γ2 channels was 25.8 ± 4.7 ms and 0.78 ± 0.03 (n = 3), respectively and for α1β2γ2 channels was 8.4 ± 1.9 ms and 0.73 ± 0.02 (n = 3), respectively. These measurements are consistent with the reported slower deactivation phase of ensemble, α3β3γ2 mediated synaptic currents and suggest that GABA has a longer occupancy at α3β3γ2 channels than at α1β2γ2 channels.