TY - JOUR
T1 - cADP ribose and [Ca2+](i) regulation in rat cardiac myocytes
AU - Prakash, Y. S.
AU - Kannan, Mathur S
AU - Walseth, Timothy F
AU - Sieck, Gary C.
PY - 2000
Y1 - 2000
N2 - cADP ribose (cADPR)-induced intracellular Ca2+ concentration ([Ca2+](i)) responses were assessed in acutely dissociated adult rat ventricular myocytes using real-time confocal microscopy. In quiescent single myocytes, injection of cADPR (0.1-10 μM) induced sustained, concentration-dependent [Ca2+](i) responses ranging from 50 to 500 nM, which were completely inhibited by 20 μM 8-amino-cADPR, a specific blocker of the cADPR receptor. In myocytes displaying spontaneous [Ca2+](i) waves, increasing concentrations of cADPR increased wave frequency up to ~ 31250% of control. In electrically paced myocytes (0.5 Hz, 5-ms duration), cADPR increased the amplitude of [Ca2+](i) transients in a concentration-dependent fashion, up to 150% of control. Administration of 8-amino-cADPR inhibited both spontaneous waves as well as [Ca2+](i) responses to electrical stimulation, even in the absence of exogenous cADPR. However, subsequent [Ca2+](i) responses to 5 mM caffeine were only partially inhibited by 8-amino-cADPR. In contrast, even under conditions where ryanodine receptor (RyR) channels were blocked with ryanodine, high cADPR concentrations still induced an [Ca2+](i) response. These results indicate that in cardiac myocytes, cADPR induces Ca2+ release from the sarcoplasmic reticulum through both RyR channels and via mechanisms independent of RyR channels.
AB - cADP ribose (cADPR)-induced intracellular Ca2+ concentration ([Ca2+](i)) responses were assessed in acutely dissociated adult rat ventricular myocytes using real-time confocal microscopy. In quiescent single myocytes, injection of cADPR (0.1-10 μM) induced sustained, concentration-dependent [Ca2+](i) responses ranging from 50 to 500 nM, which were completely inhibited by 20 μM 8-amino-cADPR, a specific blocker of the cADPR receptor. In myocytes displaying spontaneous [Ca2+](i) waves, increasing concentrations of cADPR increased wave frequency up to ~ 31250% of control. In electrically paced myocytes (0.5 Hz, 5-ms duration), cADPR increased the amplitude of [Ca2+](i) transients in a concentration-dependent fashion, up to 150% of control. Administration of 8-amino-cADPR inhibited both spontaneous waves as well as [Ca2+](i) responses to electrical stimulation, even in the absence of exogenous cADPR. However, subsequent [Ca2+](i) responses to 5 mM caffeine were only partially inhibited by 8-amino-cADPR. In contrast, even under conditions where ryanodine receptor (RyR) channels were blocked with ryanodine, high cADPR concentrations still induced an [Ca2+](i) response. These results indicate that in cardiac myocytes, cADPR induces Ca2+ release from the sarcoplasmic reticulum through both RyR channels and via mechanisms independent of RyR channels.
KW - Confocal microscopy
KW - Heart
KW - Intracellular calcium concentration
KW - Ryanodine receptor
KW - Sarcoplasmic reticulum
KW - Second messenger
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U2 - 10.1152/ajpheart.2000.279.4.h1482
DO - 10.1152/ajpheart.2000.279.4.h1482
M3 - Article
C2 - 11009432
AN - SCOPUS:0033695546
SN - 0363-6143
VL - 279
SP - H1482-H1489
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 4 48-4
ER -