Previous studies have reported that cyclic ADP-ribose (cADPR) induces Ca2+ release from the sarcoplasmic reticulum (SR) in cardiac myocytes. However, the involvement of ryanodine receptor (RyR) channels in the cADPR response remains controversial. In rat myocardium, cADPR-induced [Ca2+]i responses were assessed by: 1) measurement of [Ca2+]i in acutely dissociated myocytes using confocal microscopy; and 2) measurement of force responses in β-escin permeabilized ventricular strips. In dissociated myocytes, cADPR (0.1 to 10 μM) induced sustained, dose-dependent SR Ca2+ release, which was completely inhibited by 1 μM 8-amino cADPR, but only partially inhibited by 10 μM ryanodine. In ventricular strips, cADPR (10, 25 and 100 μM) induced sustained, dose-dependent force responses, which were completely inhibited by 50 μM 8-amino cADPR, but only partially inhibited by 10 μM ryanodine or 25 μM ruthenium red. With both ryanodine and ruthenium red, complete inhibition of RyR channels was confirmed by the lack of response to caffeine. These results indicate that in cardiac myocytes cADPR induces Ca2+ release through RyR channels. However, cADPR also appears to induce Ca2+ release through mechanisms independent of RyR channels.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology