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A Zinc—Potassium Continuum in Neuronal Apoptosis

  • Chapter
Brain Hypoxia and Ischemia

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

Intraneuronal zinc homeostasis is tightly regulated by a variety of specialized ionic transport mechanisms, metal binding proteins, and organelle com-partmentalization. Dysregulation of these processes by pathophysiological conditions, especially those in which reactive oxygen and nitrogen species (ROS, RNS) have been implicated, is central to the progression of neuronal injury. In addition to disruption of zinc homeostatic mechanisms, a reduction of intracellular ionic strength via enhanced potassium efflux is a critical and perhaps requisite mediator of apoptotic cell death induced by lethal insults to the brain. In this chapter, we describe the manner by which the cellular dysregulation of these two essential ions, zinc and potassium, lies along a signaling continuum leading to the demise of central neurons. By reviewing the current status of the field and presenting new information, we detail the molecular mechanisms linking intracellular zinc liberation to cellular potassium efflux in acute neuronal injury, such as ischemia. The complete characterization of this potentially ubiquitous cell death signaling cascade will likely provide novel therapeutic targets for cerebral ischemia and, possibly, other forms of neurodegeneration.

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Acknowledgements

This work was supported by an American Heart Association Predoctoral Fellowship to Patrick Redman, an American Heart Association Postdoctoral Fellowship to Megan Knoch, and by NIH grant NS043227 to Elias Aizenman. The technical expertise of Karen Hartnett is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Neurobiology, University of Pittsburgh School of Medicine E1456 BST, 3500 Terrace Street, Pittsburgh, PA 15261, USA

    Patrick Redman, Megan Knoch & Elias Aizenman

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  1. Patrick Redman
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  2. Megan Knoch
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  3. Elias Aizenman
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Editors and Affiliations

  1. University of California, San Diego, CA

    Gabriel G. Haddad

  2. Rady Children's Hospital, San Diego, CA

    Gabriel G. Haddad

  3. Emory University, Atlanta, GA

    Shan Ping Yu

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Redman, P., Knoch, M., Aizenman, E. (2009). A Zinc—Potassium Continuum in Neuronal Apoptosis. In: Haddad, G.G., Yu, S.P. (eds) Brain Hypoxia and Ischemia. Contemporary Clinical Neuroscience. Humana Press. https://doi.org/10.1007/978-1-60327-579-8_6

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