Routes of Zn2+ entry in ischemia

Abstract

Synaptic release of Zn2+ and its translocation into postsynaptic hippocampal pyramidal neurons may contribute to their degeneration in epilepsy or ischemia. Culture studies have revealed that of the three major routes of divalent cation entry [NMDA channels, voltage sensitive Ca2+ channels (VSCC) and Ca‐A/K channels], Ca‐A/K channels exhibit the highest permeability to exogenously applied Zn2+. Until recently, there has been little information about routes through which synaptically released Zn2+ enters postsynaptic neurons. In a recent study employing mouse hippocampal slice preparations subjected to brief oxygen and glucose deprivation (OGD), we found a Ca‐A/K channel antagonist, but not combined NMDA and VSCC antagonism, to attenuate both Zn2+ accumulation in CA3 and CA1 pyramidal neurons and their subsequent injury. While overall Zn2+ accumulation appears to reflect a combination of translocation and release from intracellular stores, present results suggest that Zn2+ influx through Ca‐A/K channels may play a critical role in Zn2+ dependent ischemic injury.