Divalent cations as modulators of neuronal excitability: Emphasis on copper and zinc

ABSTRACT Based on indirect evidence, a role for synaptically released copper and zinc as modulators of neuronal activityhas been proposed. To test this proposal directly, we studied the effect of copper, zinc, and other divalentcations on voltage-dependent currents in dissociated toad olfactory neurons and on their firing rate induced bysmall depolarizing currents. Divalent cations in the nanomolar range sped up the activation kinetics andincreased the amplitude of the inward sodium current. In the micromolar range, they caused a dose dependentinhibition of the inward Na + and Ca 2+ currents (I Na and I Ca ) and reduced de amplitude of the Ca 2+ -dependentK + outward current (I Ca-K ). On the other hand, the firing rate of olfactory neurons increased when exposed tonanomolar concentration of divalent cations and decreased when exposed to micromolar concentrations. Thisbiphasic effect of divalent cations on neuronal excitability may be explained by the interaction of these ionswith high and low affinity sites in voltage-gated channels. Our results support the idea that these ions arenormal modulators of neuronal excitability.Key terms: copper, zinc, modulators, channels, neuronal excitability