Sponsor
This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR-48911) to JJA and Portland State University to BSM.
Published In
Antioxidants and Redox Signaling
Document Type
Article
Publication Date
5-1-2007
Subjects
Oxidation-reduction reaction, Membrane proteins, Ryanodine -- Receptors, Calcium channels
Abstract
The Ca(2+) release channel (CRC) from sarcoplasmic reticulum (SR) is rich in thiol groups, and their oxidation/- reduction by thiol reagents activates/inhibits the CRC. Most channel regulators are not thiol reagents, and the mechanism of their action is illusive. Here the authors show that many channel activators act as electron acceptors, while many channel inhibitors act as electron donors in free radical reactions. The channel activator, caffeine, and the CRC inhibitor, tetracaine, are shown to interact competitively, which suggests that there exists a common site(s) on the CRC, that integrates the donor/acceptor effects of ligands. Moreover, channel activators shift the redox potential of reactive thiols on the ryanodinereceptor (RyR) to more negative values and decrease the number of reactive thiols, while channel inhibitors shift the redox potential to more positive values and increase the number of reactive thiols. These observations suggest that thenon-thiol channel modulators shift the thiol-disulfide balance within CRC by transiently exchanging electrons with the Ca(2+) release protein.
DOI
10.1089/ars.2006.1426
Persistent Identifier
http://archives.pdx.edu/ds/psu/7620
Citation Details
Marinov, B., Olojo, R., Xia, R., & Abramson, J. (2007). Non-thiol reagents regulate ryanodine receptor function by redox interactions that modify reactive thiols. Antioxidants & Redox Signaling, 9(5), 609-621.
Description
This is a copy of an article published in the Antioxidants and Redox Signaling © 2007 [copyright Mary Ann Liebert, Inc.]; Antioxidants and Redox Signaling is available online at: http://online.liebertpub.com.