Zn²⁺ Blocks the NMDA- and Ca²⁺-Triggered Postexposure Current <i>I</i> _pe in Hippocampal Pyramidal Cells

Abstract

Whole cell voltage-clamp recordings from acutely isolated hippocampal CA1 pyramidal cells from adult guinea pigs were used to evaluate divalent cations as possible blockers of the postexposure current (Ipe). Ipe is a cation current that is triggered by the rise in intracellular Ca2+ concentration that occurs after the application of a toxic level of N-methyl-D-aspartate (NMDA). Once triggered, Ipe continues to grow until death of the neuron occurs. Ipe may be a critical link between transient NMDA exposure and cell death. Ipe was blocked by micromolar concentrations of Zn2+. The Zn2+ effect had an IC50 of 64 microM and saturated at 500 microM. Prolonged Zn2+ block of Ipe revealed that the maintenance of a steady Ipe is not dependent on Ipe-mediated Ca2+ influx but that the continuous growth in Ipe is dependent on Ipe-mediated Ca2+ influx. The availability of an effective blocker of Ipe should facilitate the investigation of the intracellular activation pathway of Ipe and the role of Ipe in neuronal death.