LEVELS OF BENZODIAZEPINE RECEPTOR SUBTYPES AND GABA(A) RECEPTOR ALPHA-SUBUNIT MESSENGER-RNA DO NOT CORRELATE DURING DEVELOPMENT

Developmental changes in the pharmacological properties of the GABA(A) receptor have been suggested to result from changes in the subunit co mposition of the receptor complex. The nicotinic acetylcholine recepto r is structurally related to the GABA(A) receptor and undergoes a deve lopmental subunit switch at the neuromuscular synapse. To examine the mechanistic similarities between these systems we sought to find wheth er the changes in GABA(A) receptor subunits are controlled by changes in messenger RNA levels, as they are for the nicotinic acetylcholine r eceptor. We found a 10-fold increase in the level of alpha 1-subunit m RNA, and a small increase in levels of GABA(A)/benzodiazepine receptor s from day 1 to day 24 of rat cerebellar development. We also found th at the levels of alpha 1-subunit mRNA were higher than the levels of m RNA encoding other alpha subunits at all developmental time points. Th e low levels of messenger RNA for alpha 2, alpha 3, and alpha 5 subuni ts are inconsistent with the high levels of type II benzodiazepine bin ding in the rat cerebellum at birth because these alpha subunits have been shown to form GABA(A) receptors with type II benzodiazepine bindi ng. These findings are inconsistent with simple models that would expl ain the developmental differences in GABA(A) receptor pharmacology sim ply as a result of changes in alpha-subunit gene expression.