Journal
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Volume 88, Issue 7, Pages 702-715Publisher
CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/Y10-055
Keywords
cardiac glycosides; cardiac Na+/K+ pump; SR Ca2+ transport; Ca2+-induced Ca2+ release; SL Ca2+ channels; SL Na+/Ca2+ exchange; Ca2+ handling in cardiomyocytes.
Categories
Funding
- Canadian Institutes of Health Research
- St. Boniface General Hospital Research Foundation
Ask authors/readers for more resources
Earlier studies have demonstrated that ouabain-induced increase in [Ca2+](i), as a consequence of sarcolemma (SL) Na+/K+-ATPase inhibition, is associated with activation of both the SL Na+/Ca2+ exchanger and SL Ca2+ channels. In view of the importance of sarcoplasmic reticulum (SR) in the regulation of [Ca2+](i), this study examined the role of SR in ouabain-induced increase in [Ca2+](i) in both quiescent and KCl-depolarized cardiomyocytes. For this purpose, adult rat cardiomyocytes were loaded with fura-2 and ouabain-induced changes in [Ca2+](i) were monitored upon treatment with or without different agents that are known to influence Ca2+ handling by the intracellular organelles. Ouabain not only increased the basal [Ca2+](i) and augmented KCl-induced increase in [Ca2+](i) but also produced similar effects on the ATP-induced increase in [Ca2+](i). Treatments of cardiomyocytes with caffeine, ryanodine, or cyclopiazonic acid, which affect SR Ca2+ stores, attenuated the ouabain-induced increase in basal Ca2+ as well as augmentation of the KCl response. Both ryanodine and cyclopiazonic acid produced additional effects, when used in combination with a SL Ca2+ channel inhibitor (verapamil), but not with a Na+/Ca2+ exchange inhibitor (KB-R7943). Inhibitors of Ca2+/calmodulin kinase, protein kinase A, and inositol-3-phosphate receptors were also observed to depress the ouabain-induced increase in [Ca2+](i) in cardiomyocytes. On the other hand, mitochondrial Ca2+ transport inhibitors did not exert any effect on the ouabain-induced alterations in [Ca2+](i) in cardiomyocytes. Furthermore, ouabain did not show any direct effect on the Ca2+ uptake and Ca2+ release activities of SR or mitochondria. These results suggest an indirect involvement of SR Ca2+ stores in the ouabain-induced increase in [Ca2+](i) in cardiomyocytes and indicate the participation of both Ca2+-induced Ca2+ release and regulatory mechanisms in this action.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available