Regulation of the cardiac muscle ryanodine receptor by O(2) tension and S-nitrosoglutathione.

Journal Article

The cardiac and skeletal muscle sarcoplasmic reticulum ryanodine receptor Ca(2+) release channels contain thiols that are potential targets of endogenously produced reactive oxygen and nitrogen intermediates. Previously, we showed that the skeletal muscle ryanodine receptor (RyR1) has O(2)-sensitive thiols; only when these thiols are in the reduced state (pO(2) approximately 10 mmHg) can physiological concentrations of NO (nanomolar) activate RyR1. Here, we report that cardiac muscle ryanodine receptor (RyR2) activity also depends on pO(2), but unlike RyR1, RyR2 was not activated or S-nitrosylated directly by NO. Rather, activation and S-nitrosylation of RyR2 required S-nitrosoglutathione. The effects of peroxynitrite were indiscriminate on RyR1 and RyR2. Our results indicate that both RyR1 and RyR2 are pO(2)-responsive yet point to different mechanisms by which NO and S-nitrosoglutathione influence cardiac and skeletal muscle sarcoplasmic reticulum Ca(2+) release.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • December 30, 2008

Published In

Volume / Issue

  • 47 / 52

Start / End Page

  • 13985 - 13990

PubMed ID

  • 19053230

Pubmed Central ID

  • 19053230

Electronic International Standard Serial Number (EISSN)

  • 1520-4995

Digital Object Identifier (DOI)

  • 10.1021/bi8012627


  • eng

Conference Location

  • United States