ZN2-TRIGGERED AND CA2+-TRIGGERED POSTEXPOSURE CURRENT I-PE IN HIPPOCAMPAL PYRAMIDAL CELLS( BLOCKS THE NMDA)

Whole cell voltage-clamp recordings from acutely isolated hippocampal CA1 pyramidal cells from adult guinea pigs were used to evaluate dival ent 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 gro w until death of the neuron occurs. I-pe may be a critical link betwee n transient NMDA exposure and cell death. I-pe was blocked by micromol ar concentrations of Zn2+. The Zn2+ effect had an IC50 of 64 mu M and saturated at 500 mu M. Prolonged Zn2+ block of I-pe revealed that the maintenance of a steady I-pe is not dependent on I-pe-mediated Ca2+ in flux but that the continuous growth in I-pe is dependent on I-pe-media ted Ca2+ influx. The availability of an effective blocker of I-pe shou ld facilitate the investigation of the intracellular activation pathwa y of I-pe and the role of I-pe in neuronal death.