ZINC ENHANCES GABAERGIC TRANSMISSION IN RAT NEOCORTICAL NEURONS

1. Intracellular recordings were made in layer II-III neurons of rat n eocortical slices maintained in vitro. The effect of bath application of zinc (50-300 AM) on evoked synaptic activity and passive membrane p roperties was examined. 2. Excitatory postsynaptic potentials (EPSPs) mediated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors were re corded in response to electrical stimulation. Zinc did not affect eith er type of EPSP. Resting membrane potential, repetitive firing propert ies, and input resistance were not altered by zinc. 3. Inhibitory post synaptic potentials (IPSPs) were enhanced after zinc application. Zinc also induced generation of large amplitude spontaneousy-aminobutyric acid-, (GABA(A))- and GABA(B)-mediated IPSPs. Postsynaptic responses t o iontophoretically applied GABA were unaffected. In the presence of z inc, GABAergic synaptic potentials could result in generation of actio n 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. Und er these conditions spontaneous IPSPs with superimposed action potenti als were present. Baclofen, in the presence of zinc, reduced the ampli tude of evoked IPSPs. 5. These results indicate that zinc may be an en dogenously occurring neuromodulator. Zinc appears to enhance GABAergic IPSPs by increasing the excitability of inhibitory interneurons, thus resulting in increased GABA release.