The Journal of Neurophysiology Vol. 86 No. 4 October 2001, pp. 1652-1660
Copyright ©2001 by the American Physiological Society

Zinc and Copper Influence Excitability of Rat Olfactory Bulb Neurons by Multiple Mechanisms

Department of Biological Science, Program in Neuroscience, Florida State University, Tallahassee, Florida 32306-4340

Horning, Michelle S. and Paul Q. Trombley. Zinc and Copper Influence Excitability of Rat Olfactory Bulb Neurons by Multiple Mechanisms. J. Neurophysiol. 86: 1652-1660, 2001. Zinc and copper are highly concentrated in several mammalian brain regions, including the olfactory bulb and hippocampus. Whole cell electrophysiological recordings were made from rat olfactory bulb neurons in primary culture to compare the effects of zinc and copper on synaptic transmission and voltage-gated ion channels. Application of either zinc or copper eliminated GABA-mediated spontaneous inhibitory postsynaptic potentials. However, in contrast to the similarity of their effects on inhibitory transmission, spontaneous glutamate-mediated excitatory synaptic activity was completely blocked by copper but only inhibited by zinc. Among voltage-gated ion channels, zinc or copper inhibited TTX-sensitive sodium channels and delayed rectifier-type potassium channels but did not prevent the firing of evoked single action potentials or dramatically alter their kinetics. Zinc and copper had distinct 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 membrane potential. The effects of zinc and copper on potassium channels likely underlie their effects on repetitive firing in response to long-duration step depolarizations. Copper reduced repetitive firing independent of the initial membrane voltage. In contrast, whereas zinc reduced repetitive firing at membrane potentials associated with zinc-mediated enhancement of the A-type current (50 mV), in a significant proportion of neurons, zinc increased repetitive firing at membrane potentials associated with zinc-mediated inhibition of the A-type current (90 mV). Application of zinc or copper also inhibited voltage-gated Ca²⁺ channels, suggesting a possible role for presynaptic modulation of neurotransmitter release. Despite similarities between the effects of zinc and copper on some ligand- and voltage-gated ion channels, these data suggest that their net effects likely contribute to differential modulation of neuronal excitability.