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GABAA receptor subunit interactions important for benzodiazepine and zinc modulation: a patch-clamp and single cell RT-PCR study


: Dr Flemming Fryd Johansen, 1Laboratory of Neuro pathology, as above.


The expression of mRNAs for the GABAA receptor subunits α1, α6, β2, β3, γ2 and δ in single mouse cerebellar granule cells and cortical interneurons were analysed by RT-PCR and correlated to their midazolam and zinc modulation of agonist-induced receptor currents. The registration of molecular and electrophysiological data from each cell allowed us to estimate the significance of individual subunits and their two-factor interaction for modulation. The presence of α6 decreased midazolam modulation, but statistical analysis also suggested interactions of α6 with β3 and γ2 with respect to midazolam modulation. Zinc modulation was decreased by the presence of γ2, and analysis points to an β3 effect as well as an interaction between γ2 and δ in zinc modulation. Thus, our model confirmed, in single native cells, the known effects of α6 in midazolam and γ2 in zinc modulation, and additionally pointed to significant subunit interactions that need to be further tested in recombinant receptors. The present study offers a method to identify subunit interactions in heteromeric receptor complexes.

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