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4 subunit by GABA and pentobarbital
Department of Anaesthesiology, Campus Box 8054, 660 South Euclid Ave, Washington University, St Louis, MO 63110, USA
The activation properties of GABAA receptors containing 
4ß2
2 and 4ß2
subunits were examined in the presence of GABA or pentobarbital. The receptors were expressed transiently in HEK 293 cells, and the electrophysiological experiments were carried out using cell-attached single-channel patch clamp or whole-cell macroscopic recordings. The data show that GABA is a stronger activator of 4ß22 receptors than 4ß2 receptors. Single-channel clusters were recorded from 4ß22 receptors in the presence of 10–5000 µM GABA. The maximal intracluster open probability was 0.35, with a half-maximal response elicited by 32 µM GABA. Simultaneous kinetic analysis of single-channel currents obtained at various GABA concentrations yields a channel opening rate constant of 250 s–1, and a KD of 20 µM. In contrast, only isolated openings were observed in the presence of GABA for the 4ß2 receptor. Pentobarbital was a strong activator of both 4ß22 and 4ß2 receptors. The maximal cluster open probability, recorded in the presence of 100 µM pentobarbital, was 0.7. At higher pentobarbital concentrations, the cluster open probability was reduced, probably due to channel block. The results from single-channel experiments were confirmed by macroscopic recordings from HEK cells in the presence of GABA or pentobarbital.
(Received 17 November 2003;
accepted after revision 13 February 2004;
first published online 13 February 2004)
Corresponding author G. Akk: Department of Anaesthesiology, Washington University in St Louis, Campus Box 8054, 660 S. Euclid Ave, St Louis, MO 63110, USA. Email: akk{at}morpheus.wustl.edu
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