Oxidative modulation of K+ channels in the central nervous system in neurodegenerative diseases and aging

• Published in: Antioxidants & redox signaling Vol. 22; no. 6; p. 505
• Main Authors: Peers, Chris, Boyle, John P
• Format: Journal Article
• Language: English
• Published: United States 20.02.2015
• Subjects: Aging - metabolism; Animals; Apoptosis; Carbon Monoxide - metabolism; Central Nervous System - metabolism; Gasotransmitters - metabolism; Humans; Hydrogen Sulfide - metabolism; Neurodegenerative Diseases - metabolism; Oxidation-Reduction; Oxidative Stress; Potassium Channels - metabolism; Reactive Oxygen Species - metabolism
• DOI: 10.1089/ars.2014.6007

Oxidative stress and damage are well-established components of neurodegenerative diseases, contributing to neuronal death during disease progression. Here, we consider key K(+) channels as target proteins that can undergo oxidative modulation, describe what is understood about how this influences disease progression, and consider regulation of these channels by gasotransmitters as a means of cellular protection. Oxidative regulation of the delayed rectifier Kv2.1 and the Ca(2+)- and voltage-sensitive BK channel are established, but recent studies contest how their redox sensitivity contributes to altered excitability, progression of neurodegenerative diseases, and healthy aging. Both Kv2.1 and BK channels have recently been established as target proteins for regulation by the gasotransmitters carbon monoxide and hydrogen sulfide. Establishing the molecular basis of such regulation, and exactly how this influences excitability and vulnerability to apoptotic cell death will determine whether such regulation can be exploited for therapeutic benefit. Developing a more comprehensive picture of the oxidative modulation of K(+) channels (and, indeed, other ion channels) within the central nervous system in health and disease will enable us to better understand processes associated with healthy aging as well as distinct processes underlying progression of neurodegenerative diseases. Advances in the growing understanding of how gasotransmitters can regulate ion channels, including redox-sensitive K(+) channels, are a research priority for this field, and will establish their usefulness in design of future approaches for the treatment of such diseases.