Regulation of the cardiac muscle ryanodine receptor by O(2) tension and S-nitrosoglutathione.
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.
Sun
Junhui
J
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Yamaguchi
Naohiro
N
Xu
Le
L
Eu
Jerry P
JP
Stamler
Jonathan S
JS
Meissner
Gerhard
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010313:Partial Pressure; D030421:Peroxynitrous Acid / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000737:chemistry
D019837:Ryanodine Receptor Calcium Release Channel; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D010100:Oxygen; D002118:Calcium