Zn2+ Blocks the NMDA- and Ca2+-triggered Post-exposure Current Ipe in
Hippocampal Pyramidal Cells.
Qiang X. Chen, Katherine L. Perkins, and Robert K.S. Wong.
Department of Pharmacology, State University of New York Health Science
Center, Brooklyn, New York 11203.
APStracts 4:260N, 1997.
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 post-exposure current Ipe. Ipe is a cation current
which is triggered by the rise in intracellular Ca2+ concentration which
occurs following the application of a toxic level of 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 æM and saturated at
500 æM. Prolonged Zn2+ block of Ipe revealed that the maintenance of a steady
Ipe is not dependent upon Ipe-mediated Ca2+ influx but that the continuous
growth in Ipe is dependent upon 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.
Received 20 August 1997; accepted in final form 19 September 1997.
APS Manuscript Number J692-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997