Zinc and copper influence excitability of rat olfactory bulb neurons by multiple mechanisms

Zinc and copper are highly concentrated in several mammalian brain regions, including the olfactory bulb and hippocampus. Whole cell electrophysiologi cal recordings were made from rat olfactory bulb neurons in primary culture to compare the effects of zinc and copper on synaptic transmission and vol tage-gated ion channels. Application of either zinc or copper eliminated GA BA-mediated spontaneous inhibitory postsynaptic potentials. However, in con trast to the similarity of their effects on inhibitory transmission, sponta neous glutamate-mediated excitatory synaptic activity was completely blocke d by copper but only inhibited by zinc. Among voltage-gated ion channels, z inc or copper inhibited TTX-sensitive sodium channels and delayed rectifier -type potassium channels but did not prevent the firing of evoked single ac tion potentials or dramatically alter their kinetics. Zinc and copper had d istinct effects on transient A-type potassium currents. Whereas copper only inhibited the A-type current, zinc modulation of A-type currents resulted in either potentiation or inhibition of the current depending on the membra ne potential. The effects of zinc and copper on potassium channels likely u nderlie their effects on repetitive firing in response to long-duration ste p depolarizations. Copper reduced repetitive firing independent of the init ial membrane voltage. In contrast, whereas zinc reduced repetitive firing a t membrane potentials associated with zinc-mediated enhancement of the A-ty pe current (-50 mV), in a significant proportion of neurons, zinc increased repetitive firing at membrane potentials associated with zinc-mediated inh ibition of the A-type current (-90 mV). Application of zinc or copper also inhibited voltage-gated Ca2+ channels, suggesting a possible role for presy naptic modulation, of neurotransmitter release. Despite similarities betwee n the effects of zinc and copper on some ligand- and voltage-gated ion chan nels, these data suggest that their net effects likely contribute to differ ential modulation of neuronal excitability.