Pharmacological properties of gamma-aminobutyric acid-, glutamate-, and aspartate-induced depolarizations in cultured astrocytes.
Differentiated glial fibrillary acidic protein-positive astrocytes in homogeneous cultures of early postnatal rat cerebral hemispheres respond by membrane depolarization to gamma-aminobutyric acid (GABA), glutamate, and aspartate with a threshold concentration of approximately 10(-5) M. The GABA-induced depolarization is antagonized by two blockers of the neuronal GABAA receptor, picrotoxin and bicuculline, but is not affected by the uptake blockers beta-alanine or nipecotic acid. An agonist of the GABAA receptor, muscimol, produces a dose-response curve similar to that of GABA, whereas the agonist of the GABAB receptor, baclofen, did not alter the membrane potential. When repetitive pulses of GABA are given to one cell, its responsiveness depends on the time interval between pulses. Within 30 sec after termination of the first pulse the cell remains unresponsive to the second pulse. With increased time intervals between the pulses, reactivity toward GABA recovers. Five minutes after the first pulse the cell regains 75% of its initial depolarization peak. Aspartate results in a depolarization similar in size and time course to that induced by glutamate. The glutamate agonists, quisqualate and ibotenate, and kainate are less potent than glutamate. N-Methyl-D-aspartate has no effect on the membrane potential of astrocytes. The pharmacological features of the glutamate response are therefore similar to those of the receptor mediating neuronal glutamate transport.
Kettenmann
H
H
Schachner
M
M
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004594:Electrophysiology; D018756:GABA Antagonists; D005971:Glutamates / Q000494:pharmacology* / Q000502:physiology; D018698:Glutamic Acid; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018756:GABA Antagonists; D005971:Glutamates; D009118:Muscimol; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid