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Nitrergic modulation of ion channel function in regulating neuronal excitability

Spiers, Jereme G; Steinert, Joern R

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Jereme G Spiers


Nitric oxide (NO) signaling in the brain provides a wide range of functional properties in response to neuronal activity. NO exerts its effects through different signaling pathways, namely, through the canonical soluble guanylyl cyclase-mediated cGMP production route and via post-translational protein modifications. The latter pathways comprise cysteine S-nitrosylation and 3-nitrotyrosination of distinct tyrosine residues. Many ion channels are targeted by one or more of these signaling routes, which leads to their functional regulation under physiological conditions or facilities their dysfunction leading to channelopathies in many pathologies. The resulting alterations in ion channel function changes neuronal excitability, synaptic transmission, and action potential propagation. Transient and activity-dependent NO production mediates reversible ion channel modifications via cGMP and S-nitrosylation signaling, whereas more pronounced and longer-term NO production during conditions of elevated oxidative stress leads to increasingly cumulative and irreversible protein 3-nitrotyrosination. The complexity of this regulation and vast variety of target ion channels and their associated functional alterations presents a challenging task in assessing and understanding the role of NO signaling in physiology and disease.


Spiers, J. G., & Steinert, J. R. (2021). Nitrergic modulation of ion channel function in regulating neuronal excitability. Channels, 15(1), 666-679.

Journal Article Type Article
Acceptance Date Oct 27, 2021
Online Publication Date Nov 22, 2021
Publication Date Jan 1, 2021
Deposit Date Jan 18, 2023
Publicly Available Date Jan 18, 2023
Journal Channels
Print ISSN 1933-6950
Electronic ISSN 1933-6969
Publisher Taylor and Francis
Peer Reviewed Peer Reviewed
Volume 15
Issue 1
Pages 666-679
Keywords Biochemistry; Biophysics
Public URL
Publisher URL


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