Nerve endings from rat brain tissue release copper upon depolarization. A possible role in regulating neuronal excitability.

Membrane vesicles from rat cerebral cortex were prepared and the functional response of the GABAA receptor was followed by monitoring GABA-activated influx of the radiotracer 36Cl- ion. CuCl2 decreased GABA-activated 36Cl- influx into synaptosomal membrane vesicles. The effect of Cu2+ was concentration dependent (5-500 microM CuCl2) and occurred with saturating (1 mM) as well as low (30 microM) GABA concentrations. A similar inhibition of the responses to muscimol (30 microM) was also observed with 50 microM CuCl2. In addition, release of copper from cortical synaptosomes and median eminence was followed by atomic absorption technique. An increased release of copper into the extracellular space was observed upon depolarization with 50 mM K+. A minimal concentration of copper was estimated to be 100 microM in the synaptic cleft. These findings suggest that copper may play a role in regulating neuronal excitability.