Kinetic Properties of GABA ρ1 Homomeric Receptors Expressed in HEK293 Cells

The ρ1 subunit of the ionotropic GABA receptors is thought to contribute to the formation of the GABAC receptors with pharmacological and physiological properties distinct from those of GABAA receptors. Previous characterization of this subunit expressed in the Xenopus oocytes revealed an ion channel with slow activation and deactivation and no desensitization, quite different from the properties of GABAC receptors observed in native cells. We expressed the human ρ1 subunit in human embryonic kidney (HEK) 293 cells and quantitatively characterized the kinetic properties of these receptors using a rapid drug application device. The ρ1 subunit expressed in HEK293 cells exhibited pharmacological and kinetic properties qualitatively identical to those described when ρ1 was expressed in the oocytes. An apparent desensitizing current observed during a constant GABA application was determined to be secondary to an ECl shift. Detailed kinetic analyses and parameter estimation for a five-state kinetic model revealed that the channel is best described by a set of rate constants with a notably faster GABA unbinding Koff rate compared to the parameters proposed for the same subunit expressed in the oocytes. The same subunit expressed in hippocampal neurons showed activation and deactivation kinetics identical to the current characterized in HEK293 cells. The kinetic properties of ρ1 subunit expressed in a nonoocyte model system may be better described quantitatively by the rate constants presented here.