Differential effects of Zn2+ and Cu2+ on neuronal and glial GABAA receptors, expressed by Xenopus oocytes microtransplanted with mouse neocortex membranes.

Zn2+ and Cu2+ released from synaptic terminals, have modulatory roles in regulating neuronal excitability. Synaptic neuronal GABAARS are relatively Zn2+-insensitive, while the extrasynaptic receptors have a higher sensitivity to block. Cu2+ is thought to block GABAARS through the same mechanism as Zn2+. So far, there is no information about Zn2+ and Cu2+ effects on glial GABAARS. Here, we compared the effects of these cations on neuronal and glial GABAARS 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 μM 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 μM in control vs 290 ± 50 μM in zinc, n=6). Preliminary results of Cu2+ effects also showed a significant difference between neuronal and glial GABAARS: at 1 μM Cu2+, the percentages of remaining GABA-currents were 46.3 ± 2 % (n = 11) and 39.1 ± 1.1 (n = 10). At 100 μM 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.