Zn²⁺ and Cu²⁺ released from synaptic terminals, have modulatory roles in regulating neuronal excitability. Synaptic neuronal GABA_AR_S are relatively Zn²⁺-insensitive, while the extrasynaptic receptors have a higher sensitivity to block. Cu²⁺ is thought to block GABA_AR_S through the same mechanism as Zn²⁺. So far, there is no information about Zn²⁺ and Cu²⁺ effects on glial GABA_AR_S. Here, we compared the effects of these cations on neuronal and glial GABA_AR_S expressed by oocytes injected with synaptosomes and gliosomes. We found that while the percentage of zinc-sensitive receptors was similar in both cases, the percentage of zinc-insensitive receptors was significantly different. Indeed, at 200 mM Zn²⁺ the mean percentage (± S.E.) of GABA remaining current in synaptosome-injected oocytes was 37.4 ± 1.1% (n = 11) and in gliosome-injected oocytes was 32.6 ± 1.6% (n = 9). The EC₅₀ for GABA significantly changed from control only for neuronal receptors (EC₅₀ 140 ± 10 mM in control vs 290 ± 50 mM in zinc, n=6). Preliminary results of Cu²⁺ effects also showed a significant difference between neuronal and glial GABA_AR_S: at 1 mM Cu²⁺, the percentages of remaining GABA-currents were 46.3 ± 2% (n = 11) and 39.1 ± 1.1 (n = 10). At 100 mM Cu²⁺, the values were 18.4 ± 1.40% (n = 13) and 13.75 ± 1.5 (n = 10). These findings indicate that neuronal and glial GABA currents are affected in a different way by the two cations, suggesting a different modulatory effect at the synaptic level.