Evidence for the regulation of L-type Ca2+ channels in the heart by reactive oxygen species: mechanism for mediating pathology.
1. It is well recognized that reactive oxygen species (ROS) can activate transduction pathways to mediate pathophysiology. An increase in ROS has been implicated in a number of cardiovascular disorders. Reactive oxygen species regulate cell function through redox modification of target proteins. One of these target proteins is the L-type Ca(2+) channel. 2. There is good evidence that thiol reducing and oxidizing compounds, including hydrogen peroxide, can influence calcium channel function. The evidence for regulation of the channel protein and regulatory proteins by thiol-specific modifying agents and relevance to hypoxia and oxidative stress is presented. 3. Clinical studies suggest that calcium channel antagonists may be beneficial in reducing myocardial injury associated with oxidative stress. The identification of cysteines as possible targets for intervention during hypoxic trigger of arrhythmia or chronic pathological remodelling is discussed.
Hool
Livia C
LC
School of Biomedical Biomolecular and Chemical Sciences and The Western Australian Institute for Medical Research, The University of Western Australia, Crawley, Western Australia, Australia. lhool@cyllene.uwa.edu.au
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D003545:Cysteine / Q000378:metabolism; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D017382:Reactive Oxygen Species; D003545:Cysteine