Differences in expression of GABAA receptor subunits, but not benzodiazepine binding, in the chick brainstem auditory...

Neurons in nucleus magnocellularis (NM) and nucleus laminaris (NL) of the chick brainstem auditory system show an unusual physiological response to GABA. Examination of these nuclei using in situ hybridization for GABAA receptor subunits showed a differential expression of the gamma 2 and alpha 1 subunits. The gamma 2 subunit was found in both NM and NL, but the alpha 1 subunit was found in NL only. Like NL, other areas of the tissue section that showed labeling with the gamma 2 probe, such as the medial vestibular nucleus (VeM) and granule cells of the cerebellum (CB), also labeled with the alpha 1 probe. Thus, given that NM labeled with the gamma 2 probe, the absence of the alpha 1 subunit was unusual in this tissue. This difference in subunit composition suggests that there may also be a difference in GABA receptor function in NM compared to these neighboring areas. One feature of the GABAA receptor believed to be related to the presence of gamma 2 and alpha 1 subunits is specific pharmacological properties of the benzodiazepine modulatory site. It has been proposed that the alpha 1 subunit is necessary for producing a GABAA receptor with a benzodiazepine site that has Type I binding characteristics. The present experiments challenge this hypothesis. Based on the differential presence of the alpha 1 subunit, one would expect that GABA receptors in NM would show different benzodiazepine binding properties than NL, VeM, and CB. However, displacement of 3H-flunitrazepam binding using CL 218,872, which differentiates between the Type I and Type II receptors, showed no difference between these areas. Additionally, the relatively high affinity for CL 218,872 suggests that even NM contains Type I receptors.