Expression and Developmental Regulation of a GABAA Receptor in Cultured Murine Cells of the Oligodendrocyte Lineage

The inhibitory neurotransmitter GABA activated Cl- currents in oligodendrocytes and their precursor cells. Most of the pharmacological features of these GABA-evoked currents matched those described for the neuronal GABAA/benzodiazepine receptor complex, such as the blockade by picrotoxin and bicuculline and the enhancement by barbiturates and benzodiazepines. In contrast to the astrocytic GABA receptor, but similar to the neuronal GABAA receptor, the inverse benzodiazepine agonist DMCM decreased GABA-induced current responses. A further similarity to the neuronal receptor is the strong run-down of the current in the absence of ATP in the pipette. A difference between oligodendroglial receptors and receptors expressed on neurons and astrocytes was revealed by the dose - response curve, which indicated only one binding site for GABA or weak allosterical interactions between two putative binding sites. Thus, GABAA receptors of precursor cells and oligodendrocytes might represent a third class of GABAA receptors, in addition to those expressed by neurons and astrocytes. The density of these receptors in the membrane, as calculated on the basis of whole cell currents and membrane capacitance, decreased by a factor of 100 when cells matured along the oligodendrocyte lineage, indicating a developmental regulation of the expression of the GABA receptor.