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 γ-aminobutyric acid_B (GABA_B) receptors in area CAl 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 μM) 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 μM). The selective GABA_B receptor agonist baclofen (10 μM) 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 CAl does not result from an action of Zn²⁺ at GABA_B receptors. We suggest instead that Zn²⁺ induces GDPs by inducing synchronized discharge of GABAergic interneurons.