Functional characterization of rat ρ2 subunits expressed in HEK 293 cells

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Abstract
GABA(C) receptors are thought to be homo- or heteropentamers composed of rho1, rho2 and rho3 subunits. Previous work on rat rho2 subunits expressed in Xenopus oocytes has suggested that they do not form functional homo-oligomeric GABA(C) receptors, but do combine with rho1 or rho3 subunits to form hetero-oligomers. These findings are difficult to interpret because both human and mouse rho2 subunits do form functional homo-oligomeric receptors. Also, many regions of the rat brain express solely rho2 subunit transcripts which, according to presently available evidence, would not result in expression of functional GABA(C) receptors. We show here that homomeric rat rho2 receptors can be expressed in HEK 293 cells. Homo-oligomeric rat rho2 receptors expressed in mammalian cells matured slowly and displayed small but detectable GABA-induced currents with slow kinetics. Rat rho2 receptors also had a decreased sensitivity to picrotoxin and a marked sensitivity to the GABA(C) receptor agonist cis-aminocrotonic acid. Our results demonstrate for the first time the expression of functional homomeric rat rho2 receptors, and suggest that rho(2) subunits may contribute to brain function, including in areas not expressing other rho subunits.