The skeletal muscle calcium release channel: coupled O2 sensor and NO signaling functions.

Journal Article (Journal Article)

Ion channels have been studied extensively in ambient O2 tension (pO2), whereas tissue PO2 is much lower. The skeletal muscle calcium release channel/ryanodine receptor (RyR1) is one prominent example. Here we report that PO2 dynamically controls the redox state of 6-8 out of 50 thiols in each RyR1 subunit and thereby tunes the response to NO. At physiological pO2, nanomolar NO activates the channel by S-nitrosylating a single cysteine residue. Among sarcoplasmic reticulum proteins, S-nitrosylation is specific to RyR1 and its effect on the channel is calmodulin dependent. Neither activation nor S-nitrosylation of the channel occurs at ambient PO2. The demonstration that channel cysteine residues subserve coupled O2 sensor and NO regulatory functions and that these operate through the prototypic allosteric effector calmodulin may have general implications for the regulation of redox-related systems.

Full Text

Duke Authors

Cited Authors

  • Eu, JP; Sun, J; Xu, L; Stamler, JS; Meissner, G

Published Date

  • August 18, 2000

Published In

Volume / Issue

  • 102 / 4

Start / End Page

  • 499 - 509

PubMed ID

  • 10966111

Pubmed Central ID

  • 10966111

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/s0092-8674(00)00054-4


  • eng

Conference Location

  • United States