Random Assembly of GABA ρ1 and ρ2 Subunits in the Formation of Heteromeric GABAC Receptors

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Abstract
1. Various combinations of the ρ subunits (ρ1A, ρ1B, ρ2A, ρ2B) of GABAC receptors cloned from white perch retina were expressed in Xenopus oocytes, and electrophysiological and pharmacological methods were used to test their ability to co-assemble into heteromeric receptors. Simultaneous injection of the two subunits, irrespective of their relative proportions, led invariably to the formation of a preponderance of heteromeric receptors. 2. The GABA deactivation responses elicited from these cells could be described by a single exponential decay, and their pharmacological responses deviated significantly from those expected of a simple mixture of two homomeric ρ1 and ρ2 receptors. In contrast, a double exponential function comprising fast and slow components was required to fit the GABA deactivation responses elicited from oocytes sequentially expressing ρ1 and ρ2 subunits, a condition that favors the formation of a mixture of homomeric ρ1 and ρ2 receptors. 3. Both the GABA-response kinetics and the sensitivity to picrotoxin of the heteromeric perch ρ1Bρ2A receptor varied with the proportion of the subunit RNA injected, indicating there is no fixed stoichiometry for their co-assembly into heteromeric ρ1ρ2 receptors. 4. If native GABAC receptors in retinal neurons behave in a similar manner as in the oocyte expression system, these finding suggest that the properties of their GABAC receptors are likely to be influenced by the transcription/translation efficiency of GABA ρ subunit genes.