Cyclic ADP-ribose does not regulate sarcoplasmic reticulum Ca2+ release in intact cardiac myocytes.
Cyclic ADP-ribose (cADPR), an intracellular second messenger known to mobilize Ca2+ in sea urchin eggs, has been implicated in modulating Ca2+ release in a variety of mammalian tissues. On the basis of studies of isolated cardiac sarcoplasmic reticulum (SR) vesicles and single SR Ca2+ release channels, cADPR has also been proposed to be a modulator of SR Ca2+ release in heart. In the present study, we directly examined the ability of cADPR to trigger SR Ca2+ release and to modulate Ca(2+)-induced Ca2+ release (CICR) in intact rat ventricular myocytes. Voltage-clamped myocytes were dialyzed with up to 100 mumol/L caged cADPR and 0.6 mumol/L calmodulin along with the Ca(2+)-sensitive dye fluo 3. A step increase in the cADPR concentration induced by flash photolysis of caged cADPR neither directly triggered SR Ca2+ release nor modulated CICR in intact myocytes. In contrast, under similar conditions, extracellular application of caffeine (1 to 2.5 mmol/L) onto myocytes produced both effects. Under equivalent conditions, flash photolysis of caged cADPR-loaded sea urchin eggs resulted in large Ca2+ transients. Further, the sustained presence of high cytosolic concentrations of either cADPR or its antagonist, 8-amino-cADPR, was ineffective in altering normal CICR in myocytes. These findings indicate that cADPR does not regulate SR Ca2+ release in intact cardiac myocytes.
Guo
X
X
Department of Physiology, Emory University School of Medicine, Atlanta, Ga 30322, USA.
Laflamme
M A
MA
Becker
P L
PL
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology / Q000528:radiation effects; D000814:Aniline Compounds; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010063:Ovum / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010782:Photolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D012617:Sea Urchins; D014966:Xanthenes
D000814:Aniline Compounds; D002147:Calmodulin; D005456:Fluorescent Dyes; D014966:Xanthenes; C092958:caged cyclic ADP-ribose; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; C059715:Fluo-3; D002110:Caffeine; D002118:Calcium