Cyclic ADP-ribose does not affect cardiac or skeletal muscle ryanodine receptors.
The cardiac muscle isoform of the ryanodine receptor/Ca2+ release channel (RYR) has been proposed to be an important target of cyclic ADP-ribose (cADPR) action in mammalian cells. However, we now demonstrate that neither cADPR (0.1-5 microM), nor the related metabolites beta-NAD+ (0.1-30 mM) and ADP-ribose (0.1-5 microM), affected cardiac RYR activity as determined by [3H]ryanodine binding to cardiac sarcoplasmic reticulum (SR) vesicles. Similarly, cADPR (1 microM) failed to activate single cardiac RYR channels in planar lipid bilayers. Skeletal muscle SR [3H]ryanodine binding was also unaffected by cADPR (up to 30 microM). These results argue against a direct role for the well-characterized RYRs of cardiac or skeletal muscle in mediating cADPR-activated Ca2+ release.
Fruen
B R
BR
Department of Veterinary PathoBiology, University of Minnesota, St. Paul 55108.
Mickelson
J R
JR
Shomer
N H
NH
Velez
P
P
Louis
C F
CF
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D036563:Cyclic ADP-Ribose; D008051:Lipid Bilayers; D009124:Muscle Proteins / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013552:Swine
D015220:Calcium Channels; D008051:Lipid Bilayers; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D009243:NAD; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D000246:Adenosine Diphosphate Ribose; D002118:Calcium