Zinc modulates transient outward current gating in hippocampal neurons

The actions of zinc ions (Zn2+) on transient outward current (TOC) were studied in cultured embryonic rat hippocampal neurons and adult guinea pig CA1 neurons acutely isolated from hippocampal slices. Zn2+ (1-1000 microM) shifted both the activation and inactivation curves for the TOC in the depolarizing direction. These effects of Zn2+ were modeled, assuming a single class of binding sites for Zn2+, yielding apparent dissociation constants for Zn2+ between 10 and 35 microM. In addition, the activation kinetics of the TOC were significantly slowed by Zn2+; deactivation was slowed at the highest concentrations of Zn2. These complex actions of Zn2+ on the TOC are likely to delay repolarization and promote spontaneous activity, resulting in action potential prolongation and hyperexcitability of hippocampal neurons.