Intracellular Zn2+ accumulation enhances suppression of synaptic activity following spreading depolarization. (16th April 2013)

• Record Type: Journal Article
• Authors: Carter, Russell E.; Seidel, Jessica L.; Lindquist, Britta E.; Sheline, Christian T.; Shuttleworth, C. William
• Is Part Of: Journal of neurochemistry. Volume 125:Number 5(2013:Jun.)
• Page Start: 673
• Page End: 684
• Publication Date: 2013-04-16
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12237
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" id="jnc12237-abs-0001"> <title>Abstract</title> <p>Spreading depolarization (SD) is a feed‐forward wave that propagates slowly throughout brain tissue and recovery from SD involves substantial metabolic demand. Presynaptic Zn<sup>2+</sup> release and intracellular accumulation occurs with SD, and elevated intracellular Zn<sup>2+</sup> ([Zn<sup>2+</sup>]<sub>i</sub>) can impair cellular metabolism through multiple pathways. We tested here whether increased [Zn<sup>2+</sup>]<sub>i</sub> could exacerbate the metabolic challenge of SD, induced by KCl, and delay recovery in acute murine hippocampal slices. [Zn<sup>2+</sup>]<sub>i</sub> loading prior to SD, by transient ZnCl<sub>2</sub> application with the Zn<sup>2+</sup> ionophore pyrithione (Zn/Pyr), delayed recovery of field excitatory post‐synaptic potentials (fEPSPs) in a concentration‐dependent manner, prolonged DC shifts, and significantly increased extracellular adenosine accumulation. These effects could be due to metabolic inhibition, occurring downstream of pyruvate utilization. Prolonged [Zn<sup>2+</sup>]<sub>i</sub> accumulation prior to SD was required for effects on fEPSP recovery and consistent with this, endogenous synaptic Zn<sup>2+</sup> release during SD propagation did not delay recovery from SD. The effects of exogenous [Zn<sup>2+</sup>]<sub>i</sub> loading were also lost in slices preconditioned with repetitive SDs, implying a rapid adaptation. Together, these results suggest that [Zn<sup>2+</sup>]<sub>i</sub> loading prior to SD can provide significant additional challenge to brain tissue, and could contribute to deleterious effects of [Zn<sup>2+</sup>]<sub>i</sub> accumulation in a range of brain injury models.</p> </abstract>