Cyclic ADP-ribose-dependent Ca2+ release is modulated by free [Ca2+] in the scallop sarcoplasmic reticulum

Cyclic ADP-ribose (cADPR) elicits calcium-induced calcium release (CICR) in a variety of cell types. We studied the effect of cADPR on Ca2+ release in muscle cells by incubating SR vesicles from scallop (Pecten jacobaeus) add uctor muscle in the presence of the Ca2+ tracer fluo-3. Exposure of SR to c ADPR (20 mu M) produced Ca2+ release, which was a function of free [Ca2+] i n a range between about 150 and 1000 nM, indicating an involvement of ryano dine-sensitive Ca2+ channels. This Ca2+ release was not significantly enhan ced by calmodulin (7 mu g/ml), but it was enhanced by equimolar addition of noncyclic ADPR. Also, the Ca2+ release elicited by cADPR/ADPR was a functi on of free [Ca2+] in a range between about 150 and 3000 nM, over which Ca2 was inhibitory. cADPR self-inactivation was observed at low free [Ca2+] (a bout 150 nM), but it tended to disappear upon [Ca2+] elevation (about 250 n M). Caffeine or ryanodine induced a Ca2+ release which was ruthenium red (2 .5 mu M) sensitive at low [Ca2+]. However, the Ca2+ release induced by eith er ryanodine or cADPR was no longer ruthenium red sensitive when free [Ca2] was increased. Based on these data, a model is proposed for Ca2+ signalin g in muscle cells, where a steady-state cADPR level would trigger Ca2+ rele ase when free [Ca2+] does reach a threshold slightly above its resting leve l, hence producing cascade RyR recruitment along SR cisternae from initial Ca2+ signaling sites. (C) 1999 Academic Press.