Potentiation of depolarization-induced calcium release from skeletal muscle triads by cyclic ADP-ribose and inositol 1,4,5-trisphosphate.

Two second messengers, cyclic ADP-ribose (cADPR) and inositol 1,4,5-trisphosphate (IP3), potentiated the Ca2+ release from sarcoplasmic reticulum induced by transverse tubular membrane depolarization monitored in a triadic vesicle prepared from skeletal muscle. However, without depolarization they could not trigger the Ca2+ release. On the contrary, only cADPR potentiated caffeine-induced Ca2+ release. Because Ca2+ releases potentiated by cADPR and IP3 were inhibited by 1 microM ruthenium red and 100 microM ryanodine, probably these second messengers potentiated the Ca2+ release through ryanodine receptor Ca2+ channels. These results suggest that in skeletal excitation-contraction coupling, cADPR and IP3 play a role as a potentiator or a modifier in vivo, but both modification pathways are different from each other.