Cyclic ADP-Ribose Does Not Regulate Sarcoplasmic Reticulum Ca 2+ Release in Intact Cardiac Myocytes

Circulation Research - Tập 79 Số 1 - Trang 147-151 - 1996
Xiaoqing Guo1, Michael A. Laflamme2, Peter L. Becker2
1Department of Physiology, Emory University School of Medicine, Atlanta, GA, 30322 USA
2the Department of Physiology, Emory University School of Medicine, Atlanta, Ga.

Tóm tắt

Cyclic ADP-ribose (cADPR), an intracellular second messenger known to mobilize Ca 2+ in sea urchin eggs, has been implicated in modulating Ca 2+ release in a variety of mammalian tissues. On the basis of studies of isolated cardiac sarcoplasmic reticulum (SR) vesicles and single SR Ca 2+ release channels, cADPR has also been proposed to be a modulator of SR Ca 2+ release in heart. In the present study, we directly examined the ability of cADPR to trigger SR Ca 2+ release and to modulate Ca 2+ -induced Ca 2+ release (CICR) in intact rat ventricular myocytes. Voltage-clamped myocytes were dialyzed with up to 100 μmol/L caged cADPR and 0.6 μmol/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 Ca 2+ 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 Ca 2+ 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 Ca 2+ release in intact cardiac myocytes.

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Circulation Research

Tập 79 Số 1

147-151

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