Molecular modulation of recombinant rat alpha(1)beta(2)gamma(2) GABA(A) receptor channels by diazepam

Recombinant gamma-aminobutyric acid (GABA(A)) receptor channels containing alpha(1)beta(2)gamma(2)-subunits were transiently expressed in HEK293 cells . Modulation by diazepam (DZ) was investigated using the patch-clamp techni que with a device for ultra-fast solution exchange. GABA activated Cl--curr ents were potentiated when DZ > 0.1 mu M was added to non-saturating concen trations of GABA (<0.1 mM GABA). Maximal potentiation of the peak current a mplitude by a factor of 2.5 was observed when 1 mu M DZ was added to the te st-solution. Deactivation of GABA-activated currents after the end of GABA pulses was best fitted with two time constants. After application of DZ + G ABA, increase of time constants of deactivation was measured. It was indepe ndent on GABA concentration. We conclude that prolongation of deactivation after application of GABA + DZ may be an important mechanism of the modulat ory action of DZ at GABA(A) receptor channels. (C) 1998 Elsevier Science Ir eland Ltd. All rights reserved.