Assembly of functional α6β3γ2δ GABAA receptors in vitro

Transgenic mice deficient in the alpha6 subunit of the GABA(A) receptor show reduced levels of the delta subunit protein and an altered GABA(A) receptor pharmacology, suggesting selective assembly mechanisms. delta reduced the binding of [H-3]Ro 15-4513 or t-butylbicyclophosphoro[S-35]thionate and, to a lesser extent, [H-3]muscimol to recombinant alpha1 beta1 gamma2(delta), alpha4 beta1 gamma2(delta) and alpha6 beta1 gamma2(delta) receptors, paralleled by diminished GABA-evoked maximal currents in electrophysiological recordings for the latter one. The delta subunit gave rise to a lower EC50 for GABA and a slowed desensitization indicating its assembly in alpha6 beta2 delta, alpha6 beta1 gamma2 delta and alpha6 beta2 gamma2 delta receptors. The data show that the delta subunits assemble in various functional GABA(A) receptor subtypes in vitro to reduce GABA-evoked maximal currents and ligand binding, but increase the potency for GABA. NeuroReport 11:4103-4106 (C) 2000 Lippincott Williams & Wilkins.