GIANT GABA(B)-MEDIATED SYNAPTIC POTENTIALS INDUCED BY ZINC IN THE RAT HIPPOCAMPUS - PARADOXICAL EFFECTS OF ZINC ON THE GABA(B) RECEPTOR

The interaction of zinc with pre- and postsynaptic GABA(B) receptors was studied in adult rat hippocampal slices using intracellular recording in CA1 and CA3 pyramidal neurons. Zinc (50 - 300 muM) antagonized baclofen responses with a variable potency, whereas CGP-35348 (100 muM) or barium (300 muM) produced a more substantial and consistent inhibition. Zinc also induced giant GABA(A)-mediated depolarizing potentials (GDP) in these neurons. After blocking GABA(A) and excitatory synaptic transmission, monosynaptic hyperpolarizing inhibitory postsynaptic potentials (IPSP) mediated by GABA(B) receptors (IPSP(B)) were inhibited by CGP-35348 or barium; however, zinc increased the latency and prolonged the duration of the IPSP(B) and also induced the appearance of spontaneous giant GABA(B)-Mediated hyperpolarizing potentials (GHP). In some cells, IPSP(B)s in zinc exhibited a multiphasic appearance. The early component was partially inhibited by 300 muM zinc and was followed by a late GHP. CGP-35348 at 100 muM inhibited the early monosynaptic IPSP(B) but not the GHP; however, at 300 muM both components were blocked. Paired-pulse inhibition of the IPSP(B) was used to assess the effect of zinc on presynaptic GABA(B) receptors. Neither the zinc-chelating agent CP94 (400 muM) nor zinc affected this phenomenon. CGP-35348, barium and polyvalent cations, such as cadmium, copper, cobalt, manganese, iron and aluminium, failed to induce giant potentials in hippocampal neurons. It is concluded that zinc is apparently unique in synchronizing the release of GABA to produce GDPs and GHPs.