Cultured astrocytes from cerebral hemispheres of early postnatal rats responded to γ-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+]0 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°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 response18 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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Neurology
- Developmental Biology
- γ-aminobutyric acid(GABA)