Zinc enhances GABAergic transmission in rat neocortical neurons.

1. Intracellular recordings were made in layer II-III neurons of rat neocortical slices maintained in vitro. The effect of bath application of zinc (50-300 microM) on evoked synaptic activity and passive membrane properties was examined. 2. Excitatory postsynaptic potentials (EPSPs) mediated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors were recorded in response to electrical stimulation. Zinc did not affect either type of EPSP. Resting membrane potential, repetitive firing properties, and input resistance were not altered by zinc. 3. Inhibitory postsynaptic potentials (IPSPs) were enhanced after zinc application. Zinc also induced generation of large amplitude spontaneous gamma-aminobutyric acid-A (GABAA)- and GABAB-mediated IPSPs. Postsynaptic responses to iontophoretically applied GABA were unaffected. In the presence of zinc, GABAergic synaptic potentials could result in generation of action potentials. 4. Directly evoked IPSPs recorded in the presence of the excitatory amino acid receptor blockers 6-cyano-7-nitroquinoxaline-2,3-dione and 2-amino-5-phosphonovaleric acid were enhanced by zinc. Under these conditions spontaneous IPSPs with superimposed action potentials were present. Baclofen, in the presence of zinc, reduced the amplitude of evoked IPSPs. 5. These results indicate that zinc may be an endogenously occurring neuromodulator. Zinc appears to enhance GABAergic IPSPs by increasing the excitability of inhibitory interneurons, thus resulting in increased GABA release.