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(Stroke. 2007;38:670.)
© 2007 American Heart Association, Inc.

Glutamate-Independent Calcium Toxicity: Introduction

Extracellular Zinc Protects Against Acidosis-Induced Injury of Cells Expressing Ca²⁺-Permeable Acid-Sensing Ion Channels

Jessica G. Hey, BS; Xiang-Ping Chu, MD, PhD; Joshua Seeds, MSc; Roger P. Simon, MD Zhi-Gang Xiong, MD, PhD

From Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Ore.

Correspondence to Zhigang Xiong, MD, PhD, Robert S. Dow, Neurobiology Laboratories, Legacy Clinical Research Center, 1225 NE 2nd Ave, Portland, OR 97232. E-mail zxiong{at}Downeurobiology.org

Abstract

Acidosis is a common feature of neurological conditions including brain ischemia, epileptic seizures, and neurotrauma. Activation of Ca²⁺-permeable acid-sensing ion channels (ASIC1a) is involved in acidosis-mediated ischemic brain injury. Zn²⁺ is a divalent cation concentrated in nerve terminals in various brain regions, and is released into the extracellular space during excitatory stimulation. Our previous studies have demonstrated that the activities of ASIC1a containing channels and acid-induced increased intracellular Ca²⁺ concentrations are inhibited dramatically by the physiological concentration of extracellular Zn²⁺. In this report, we demonstrate that decreasing the concentration of the extracellular Zn²⁺ significantly enhances acid-induced injury of HEK 293 cells, a cell line expressing homomeric ASIC1a-like channels, whereas increasing the concentration of extracellular Zn²⁺ appears to be protective. Although increased concentrations of intracellular Zn²⁺ have been shown to be detrimental to neurons, our findings may suggest that the physiological concentration of extracellular Zn²⁺ might play a protective role in acidosis-induced, ASIC1a-mediated neuronal injury.

Key Words: acid • cell injury • HEK293 • zinc

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