Effects of Zinc on Spontaneous Miniature GABA Release in Rat Hippocampal CA3 Pyramidal Neurons

Effects of Zinc on Spontaneous Miniature GABA Release in Rat Hippocampal CA3 Pyramidal Neurons

The effects of Zn<SUP>2&#8290; </SUP>on spontaneous glutamate and GABA release were tested in mechanically dissociated rat CA3 pyramidal neurons which retained functional presynaptic nerve terminals. The spontaneous miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) were pharmacologically isolated and recorded using whole-cell patch clamp technique under voltage-clamp conditions. Zn<SUP>2&#8290;</SUP> at a lower concentration (30μM) increased GABAergic mIPSC frequency without affecting mIPSC amplitude, but it decreased both mIPSC frequency and amplitude at higher concentrations (≥300μM). In contrast, Zn<SUP>2&#8290;</SUP> (3 to 100μM) did not affect glutamatergic mEPSCs, although it slightly decreased both mIPSC frequency and amplitude at 300μM concentration. Facilitatory effect of Zn<SUP>2&#8290;</SUP> on GABAergic mIPSC frequency was occluded either in Ca<SUP>2&#8290;</SUP>-free external solution or in the presence of 100μM 4-aminopyridine, a non-selective K<SUP>&#8290;</SUP> channel blocker. The results suggest that Zn<SUP>2&#8290;</SUP> at lower concentrations depolarizes GABAergic nerve terminals by blocking K<SUP>&#8290;</SUP> channels and increases the probability of spontaneous GABA release. This Zn<SUP>2&#8290;</SUP>-mediated modulation of spontaneous GABAergic transmission is likely to play an important role in the regulation of neuronal excitability within the hippocampal CA3 area.