Work

Regulation of the Cardiac Muscle Ryanodine Receptor by O2Tension andS-Nitrosoglutathione

Year: 2008

Type: article

Abstract: 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.

Source: Biochemistry

DOI: 10.1021/bi8012627

Authors: Junhui Sun, Naohiro Yamaguchi, Le Xu, Jerry P. Eu, Jonathan S. Stamler, Gerhard Meissner

Institutions: University of North Carolina at Chapel Hill, Duke University, Duke Medical Center

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases