The GABAA receptors show a large degree of structural heterogeneity, with seven different subunit families, and sixteen different subtypes in mammalian species. The family is the largest, with six different subtypes. The 1 and 6 subtypes are among the most diverse within this family and confer distinct pharmacological properties to recombinant and neuronal receptors. To determine whether different single channel and macroscopic kinetic properties were also associated with these subtypes, the 1 or 6 subunit was expressed in mammalian cells along with 3 and 2L subunits and the kinetic properties examined with outside-out patch recordings. The 132L receptors responded to GABA with long duration openings organized into multi-opening bursts. In contrast, channel openings of the 632L receptors were predominately short in duration and occurred as isolated, single openings. The subunit subtype also affected the deactivation rate of the receptor, which was almost 2-fold slower for 632L, compared to the 132L isoform. Onset of fast desensitization did not differ between the isoforms. To determine the structural domains responsible for these differences in kinetic properties, we constructed six chimeric subunits, combining different regions of the 1 and 6 subunits. The properties of the chimeric subunits indicated that structures within the third transmembrane domain (TM3) and the TM3-TM4 intracellular loop conferred differences in single channel gating kinetics that subsequently affected the deactivation rate and GABA EC50. The effect of agonist concentration on the rise time of the current showed that the extracellular N-terminal domain was largely responsible for binding characteristics, while the transmembrane domains determined the activation rate at saturating GABA concentrations. This suggests that structures outside of the agonist binding and pore-lining domains are responsible for kinetic differences conferred by the 1 and 6 subtypes. Structural heterogeneity within these transmembrane and intracellular regions can therefore influence the characteristics of the post-synaptic response of GABAA receptors with different subunit composition.