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Published Online: 28 July 2014

Redox Regulation of Neuronal Voltage-Gated Calcium Channels

Publication: Antioxidants & Redox Signaling
Volume 21, Issue Number 6

Abstract

Significance: Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Recent Advances: Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. Critical Issues: A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Future Directions: Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain. Antioxid. Redox Signal. 21, 880–891.

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Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 21Issue Number 6August 20, 2014
Pages: 880 - 891
PubMed: 24161125

History

Published in print: August 20, 2014
Published online: 28 July 2014
Published ahead of print: 25 October 2013
Published ahead of production: 8 September 2013
Accepted: 7 September 2013
Received: 29 August 2013

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    Slobodan M. Todorovic
    Department of Anesthesiology, University of Virginia School of Medicine, Charlottesville, Virginia.
    Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia.
    Vesna Jevtovic-Todorovic
    Department of Anesthesiology, University of Virginia School of Medicine, Charlottesville, Virginia.
    Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia.

    Notes

    Address correspondence to:Dr. Slobodan M. TodorovicDepartment of AnesthesiologyUniversity of Virginia School of MedicineMail Box 800710Charlottesville, VA 22908-0710E-mail: [email protected]

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