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Voltage-Gated Potassium Channels at the Crossroads of Neuronal Function, Ischemic Tolerance, and Neurodegeneration

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Abstract

Voltage-gated potassium (Kv) channels are widely expressed in the central and peripheral nervous system and are crucial mediators of neuronal excitability. Importantly, these channels also actively participate in cellular and molecular signaling pathways that regulate the life and death of neurons. Injury-mediated increased K+ efflux through Kv2.1 channels promotes neuronal apoptosis, contributing to widespread neuronal loss in neurodegenerative disorders such as Alzheimer's disease and stroke. In contrast, some forms of neuronal activity can dramatically alter Kv2.1 channel phosphorylation levels and influence their localization. These changes are normally accompanied by modifications in channel voltage dependence, which may be neuroprotective within the context of ischemic injury. Kv1 and Kv7 channel dysfunction leads to neuronal hyperexcitability that critically contributes to the pathophysiology of human clinical disorders such as episodic ataxia and epilepsy. This review summarizes the neurotoxic, neuroprotective, and neuroregulatory roles of Kv channels and highlights the consequences of Kv channel dysfunction on neuronal physiology. The studies described in this review thus underscore the importance of normal Kv channel function in neurons and emphasize the therapeutic potential of targeting Kv channels in the treatment of a wide range of neurological diseases.

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Acknowledgments

We wish to thank our colleague Edwin Levitan (University of Pittsburgh School of Medicine), whose input has been essential to our K+ channel work over the years. We would also like to acknowledge the work of current and prior members of the Aizenman Laboratory who have critically contributed to the development of our research program in this area, including Sumon Pal, BethAnn McLaughlin, Megan Knoch, Hirokazu Hara, Mandar Aras, Patrick Redman, Callie Norris, Mia Jefferson, Karen Hartnett, Kai He, and Meghan McCord. We thank Shan Ping Yu (Emory University), Dennis Choi (SUNY, Stony Brook), and John Cidlowski (NIEHS) for illuminating discussions during our early work in this field. Finally, we thank Dandan Sun and Kristopher T. Kahle for inviting us to contribute to this special issue of Translational Stroke Research. Our work has been supported by the National Institutes of Health (grant NS043277). Ms. Hegde Shah is supported by a predoctoral award from the American Heart Association (12PRE11070001).

Conflict of Interest

Niyathi Hegde Shah and Elias Aizenman declare that they have no conflict of interest.

Compliance with Ethics Requirements

This is a review article and thus there are no new experiments described that utilize human or animal subjects.

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

    Niyathi Hegde Shah & Elias Aizenman

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  1. Niyathi Hegde Shah
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  2. Elias Aizenman
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Correspondence to Niyathi Hegde Shah or Elias Aizenman.

Additional information

Invited review for Special Issue: “Ion transporters and glutamate receptor-independent mechanisms for ischemic and/or traumatic brain injury.” Guest editors: Dandan Sun & Kristopher Kahle, Translational Stroke Research.

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Shah, N.H., Aizenman, E. Voltage-Gated Potassium Channels at the Crossroads of Neuronal Function, Ischemic Tolerance, and Neurodegeneration. Transl. Stroke Res. 5, 38–58 (2014). https://doi.org/10.1007/s12975-013-0297-7

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  • DOI: https://doi.org/10.1007/s12975-013-0297-7

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