Fibrous and protoplasmic astrocytes express GABAA 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 GABAA 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 GABAA 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 astrocytes 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-beta-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 GABAA receptors that differ pharmacologically and likely differ also in subunit composition.
Rosewater
K
K
Department of Neurology, Yale University, School of Medicine, New Haven, CT 06510.
Sontheimer
H
H
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D001463:Barbiturates / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D004594:Electrophysiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000096:biosynthesis* / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001463:Barbiturates; D002243:Carbolines; D003292:Convulsants; D018080:Receptors, GABA-B; D001569:Benzodiazepines; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D005680:gamma-Aminobutyric Acid