Zn2+ Blocks the NMDA- and Ca2+-Triggered Postexposure Current I pe in Hippocampal Pyramidal Cells

Chen, Qiang X., Katherine L. Perkins, and Robert K. S. Wong. Zn2+ blocks the NMDA- and Ca2+-triggered postexposure current I pe in hippocampal pyramidal cells. J. Neurophysiol. 79: 1124–1126, 1998. 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 ( I pe). I pe 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, I pe continues to grow until death of the neuron occurs. I pe may be a critical link between transient NMDA exposure and cell death. I pe was blocked by micromolar concentrations of Zn2+. The Zn2+ effect had an IC50 of 64 μM and saturated at 500 μM. Prolonged Zn2+ block of I pe revealed that the maintenance of a steady I pe is not dependent on I pe-mediated Ca2+ influx but that the continuous growth in I pe is dependent on I pe-mediated Ca2+ influx. The availability of an effective blocker of I pe should facilitate the investigation of the intracellular activation pathway of I pe and the role of I pe in neuronal death.