Fibrous and protoplasmic astrocytes express GABA_A receptors that differ in benzodiazepine pharmacology

Astrocytes cultured from spinal cord contain two morphologically distinguishable types of astrocytes: fibrous and protoplasmic cells. Both astrocyte subtypes, in culture, are able to express GABA_A receptors, and their activation results in inward currents at the resting potential. Using patch-clamp electrophysiology we characterized their basic receptor pharmacology and compared it to spinal cord neurons that were also present in small numbers in these cultures. As in neuronal GABA_A receptors, the local anesthetic pentobarbital effectively potentiated GABA-induced currents in both astrocyte subtypes. Similarly, the benzodiazepine diazepam, on average doubled GABA-induced currents in both astrocyte subtypes. In contrast to these effects that were similar in both astrocytes types and similar to spinal cord neurons, the response to the convulsant methyl-4-ethyl-6,7-dimethoxy-β-carboline-3-carboxylate (DMCM), which is an inverse benzodiazepine agonist differs between astrocyte subtypes. DMCM reduced GABA-induced currents by about 50% in fibrous astrocytes as we also observed with spinal cord neurons. In contrast, DMCM increased GABA currents in protoplasmic astrocytes by up to 150%, an effect never observed in neurons. DMCM potentiations of GABA currents have recently been attributed to differences in receptor subunit composition. Our results thus indicate that subtypes of astrocytes express GABA_A receptors that differ pharmacologically and likely differ also in subunit composition.