Neuroscience Letters, 47 (1984) 271-276 271 Elsevier Scientific Publishers Ireland Ltd. NSL 02722 DEPOLARIZATION OF CULTURED OLIGODENDROCYTES BY GLUTAMATE AND GABA H. KETTENMANN, P. GILBERT and M. SCHACHNER Department of Neurobiology, University of Heidelberg, Im Neuenheimer Feld 504, D-6900 Heidelberg (F.R.G.) (Received February 13th, 1984; Revised version received and accepted March 12th, 1984) Key words." mouse - oligodendrocyte - neuroglia - cell culture - neurotransmitter - glutamate - ,y-aminobutyric acid Subpopulations of cultured oligodendrocytes from mouse spinal cord respond with depolarization to glutamate and GABA. Heterogeneity in the oligodendrocyte population was indicated by the observation that some cells respond to both GABA and glutamate, while others respond to only one and some are not responsive to either. Depolarizations are not mediated by an increase of [K+]o released from neurons. The response to GABA was blocked in Na ÷ -free solution and is not accompanied by a change in input resistance. Several other neurotransmitters did not induce changes in membrane potential. GABA and glutamate are prominent transmitters in the central nervous system [12]. Whereas their mechanisms of action on neurons has been extensively studied [1,4], their effect on glial cells has received comparatively little attention. Wardell [19] found no response of cultured glial cells of the cerebellum to glutamate. In a study on glial cells of the pericruciate cortex of the cat, Krnjevic and Schwartz [11] found a depolarizing effect of GABA, but not glutamate, on approximately 60°7o of the cells studied. Since the depolarization was not accompanied by a change in membrane resistance these authors suggested that the depolarization resulted from GABA uptake. Glial cells of the guinea pig olfactory cortex were later found to respond with depolarization both to glutamate and GABA [3]. The effect was attributed to K ÷ release from adjacent neurons which were thought to be the primary target of the transmitters [3,15]. An effect of neuronal K ÷ release was excluded in neuron-free systems. Tang and Orkand [18] found glutamate induced depolarization of glial cells in denervated Necturus optic nerve. Reiser and Hamprecht [13] described a bradykinin-induced hyperpolarization of cultured rat glioma cells. In primary cultures of rat brain, however, several neurotransmitters did not directly affect the membrane potential of astrocytes [8]. The goal of the present study was to characterize the effects of GABA, glutamate and other neurotransmitters on another glial subpopulation in culture, the oligodendrocytes. 0304-3940/84/$ 03.00 © 1984 Elsevier Scientific Publishers Ireland Ltd.