Action of baclofen, GABA and antagonists on the membrane potential of cultured astrocytes of rat spinal cord.
The action of gamma-aminobutyric acid A (GABAA) and B (GABAB)-agonists has been studied on the membrane potential of astrocytes in explant cultures of rat spinal cord by means of intracellular microelectrode recordings. The GABAB-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 GABAB-antagonist 5-hydroxysaclofen (10(-4) M). GABA and the GABAA-agonist muscimol (10(-4) and 10(-3) M) depolarized approximately two thirds of the glial cells tested, whereas the remaining third remained unaffected. The GABAA-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 GABAA-receptor is different from the neuronal GABAA-receptor. Our electrophysiological investigations together with recent autoradiographic binding studies strongly suggest the existence of GABAB-receptors on astrocytes whereas there is less evidence for GABAA-sites on these cells.
Hösli
L
L
Department of Physiology, University of Basel, Switzerland.
Hösli
E
E
Redle
S
S
Rojas
J
J
Schramek
H
H
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D001345:Autoradiography; D001418:Baclofen / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D018756:GABA Antagonists; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009118:Muscimol / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018756:GABA Antagonists; D009943:Organophosphorus Compounds; C061388:3-aminopropylphosphinic acid; C067367:5-hydroxysaclofen; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D001640:Bicuculline