Action of baclofen, GABA and antagonists on the membrane potential of cultured astrocytes of rat spinal cord

Abstract

The action of γ-aminobutyric acid A (GABA A) and B (GABA B)-agonists has been studied on the membrane potential of astrocytes in explant cultures of rat spinal cord by means of intracellular microelectrode recordings. The GABA B-agonists (−)-baclofen and CGP 27 492 (3-aminopropyl phosphonous acid; 10 −6 to 10 −4 M) caused a hyperpolarization of the majority of astrocytes studied. On approximately 25% of the cells, the compounds had no effect. The hyperpolarization by baclofen (10 −4 M) was reversibly antagonized by the GABA B-antagonist 5-hydroxysaclofen (10 −4 M). GABA and the GABA A-agonist muscimol (10 −4 and 10 −3 M) depolarized approximately two thirds of the glial cells tested, whereas the remaining third remained unaffected. The GABA A-antagonist bicuculline (10 −4 and 10 −3 M) only reduced the depolarization by GABA (10 −4 M) but did not completely block it. On half of the cells tested, the depolarization by GABA was not affected by bicuculline, suggesting that the glial GABA A-receptor is different from the neuronal GABA A-receptor. Our electrophysiological investigations together with recent autoradiographic binding studies strongly suggest the existence of GABA B-receptors on astrocytes whereas there is less evidence for GABA A-sites on these cells.