Premium
GABA A receptor subunit interactions important for benzodiazepine and zinc modulation: a patch‐clamp and single cell RT‐PCR study
Author(s) -
Alsbo Carsten W.,
Kristiansen Uffe,
Møller Flemming,
Hansen Suzanne L.,
Johansen Flemming Fryd
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01539.x
Subject(s) - gabaa receptor , benzodiazepine , patch clamp , protein subunit , receptor , chemistry , modulation (music) , cell , neuroscience , biophysics , microbiology and biotechnology , pharmacology , psychology , biology , biochemistry , gene , physics , acoustics
The expression of mRNAs for the GABA A receptor subunits α 1 , α 6 , β 2 , β 3 , γ 2 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 α 6 decreased midazolam modulation, but statistical analysis also suggested interactions of α 6 with β 3 and γ 2 with respect to midazolam modulation. Zinc modulation was decreased by the presence of γ 2 , and analysis points to an β 3 effect as well as an interaction between γ 2 and δ in zinc modulation. Thus, our model confirmed, in single native cells, the known effects of α 6 in midazolam and γ 2 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.