gamma-Aminobutyric acid opens Cl-channels in cultured astrocytes.
Cultured astrocytes from cerebral hemispheres of early postnatal rats responded to gamma-aminobutyric acid (GABA) with membrane depolarization. This depolarization was affected by changes in extracellular [Cl-] and depended on the membrane potential. The reversal potential of the GABA-induced depolarization was determined by double electrode voltage clamp or depolarization by elevated [K+]o and ranged between -38 and -53 mV. Cell input resistance decreased after addition of GABA with the same time course as the membrane depolarization. GABA responses were temperature dependent yielding a peak at about 14 degrees C. At higher temperatures a decrease in the GABA-induced depolarization was seen indicating that the depolarization may not be mediated by an enzyme-coupled carrier system. Addition of ouabain at different temperatures did not change the size of the GABA depolarization. This excludes the possibility that an electrogenic component of the temperature-sensitive Na+,K+-ATPase activity causes the decrease in GABA-dependent depolarization at higher temperatures. Intracellular [Cl-] was measured with Cl- sensitive microelectrodes and found to be higher than the value calculated for a free distribution according to the Nernst equation (-40 mV). Addition of furosemide did not alter the reversal potential, but reduced the size of the GABA-induced membrane depolarization. From these observations and previous experiments on the pharmacological properties of the membrane response we conclude that the ionic mechanism underlying the GABA-dependent membrane depolarization of astrocytes results from a transient increase in Cl- -conductance similar to that of the neuronal GABAA-receptor.
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D004553:Electric Conductivity; D004563:Electrochemistry; D005665:Furosemide / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D007473:Ion Channels; D005680:gamma-Aminobutyric Acid; D010042:Ouabain; D005665:Furosemide