INDUCTION OF GIANT DEPOLARIZING POTENTIALS BY ZINC IN AREA CA1 OF THE RAT HIPPOCAMPUS DOES NOT RESULT FROM BLOCK OF GABA-B RECEPTORS

The possibility that zinc (Zn2+) induces giant depolarizing potentials (GDPs) by blocking pre- and postsynaptic gamma-aminobutyric acid(B) (GABA(B)) receptors in area CA1 of rat hippocampal slices was investigated. Monosynaptic GABA(A) receptor-mediated fast and GABA(B) receptor-mediated late inhibitory postsynaptic potentials (IPSPs) were evoked in the presence of the excitatory amino acid (EAA) receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). Addition of Zn2+ (0.3 mM) resulted in the appearance of long-lasting GDPs which obscured monosynaptic late IPSPs. The GABA(A) receptor antagonist bicuculline methiodide (BMI; 30-m-M) blocked fast monosynaptic IPSPs and GDPs, revealing a monosynaptic late IPSP that was prolonged in the presence of Zn2+ and blocked by the GABA(B) receptor antagonist CGP 35 348 (100-mu-M). The selective GABA(B) receptor agonist baclofen (10-mu-M) depressed monosynaptic IPSPs and population excitatory postsynaptic potentials (pEPSPs) by acting at presynaptic GABA(B) receptors. Depression of synaptic potentials by baclofen was unaffected by Zn2+. These results suggest that induction of GDPs in area CA1 does not result from an action of Zn2+ at GABA(B) receptors. We suggest instead that Zn2+ induces GDPs by inducing synchronized dischare of GABAergic interneurons.