Random assembly of GABA rho1 and rho2 subunits in the formation of heteromeric GABA(C) receptors.

1. Various combinations of the rho subunits (rho(1A), rho(1B), rho(2A), rho(2B)) of GABA(C) 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 rho(1) and rho(2) 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 rho(1) and rho(2) subunits, a condition that favors the formation of a mixture of homomeric rho(1) and rho(2) receptors. 3. Both the GABA-response kinetics and the sensitivity to picrotoxin of the heteromeric perch rho(1B)rho(2A) receptor varied with the proportion of the subunit RNA injected, indicating there is no fixed stoichiometry for their co-assembly into heteromeric rho(1)rho(2) receptors. 4. If native GABA(C) receptors in retinal neurons behave in a similar manner as in the oocyte expression system, these finding suggest that the properties of their GABA(C) receptors are likely to be influenced by the transcription/translation efficiency of GABA rho subunit genes.