Levels of Benzodiazepine Receptor Subtypes and GABAA Receptor α-Subunit mRNA Do Not Correlate During Development

Abstract: Developmental changes in the pharmacological properties of the GABA_A receptor have been suggested to result from changes in the subunit composition of the receptor complex. The nicotinic acetylcholine receptor is structurally related to the GABA_A receptor and undergoes a developmental subunit switch at the neuromuscular synapse. To examine the mechanistic similarities between these systems we sought to find whether the changes in GABA_A receptor subunits are controlled by changes in messenger RNA levels, as they are for the nicotinic acetylcholine receptor. We found a 10-fold increase in the level of α1-subunit mRNA, and a small increase in levels of GABA_A/benzodiazepine receptors from day 1 to day 24 of rat cerebellar development. We also found that the levels of α1-subunit mRNA were higher than the levels of mRNA encoding other α subunits at all developmental time points. The low levels of messenger RNA for α2, α3, and α5 subunits are inconsistent with the high levels of type II benzodiazepine binding in the rat cerebellum at birth because these α subunits have been shown to form GABA_A receptors with type II benzodiazepine binding. These findings are inconsistent with simple models that would explain the developmental differences in GABA_A receptor pharmacology simply as a result of changes in α-subunit gene expression.