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Updated: Aug 20, 2026

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
TNF-alpha as a potential mediator of cardiac dysfunction due to intracellular Ca2+-overload
Ming Zhang1, Yan-Jun Xu, Harjot K Saini
1Department of Physiology, St. Boniface General Hospital Research Center, Institute of Cardiovascular Sciences, Faculty of Medicine University of Manitoba, Winnipeg, Canada.
Abstract:
TNF-alpha has been shown to be involved in cardiac dysfunction during ischemia/reperfusion injury; however, no information regarding the status of TNF-alpha production in myocardial injury due to intracellular Ca2+-overload is available in the literature. The intracellular Ca2+-overload was induced in the isolated rat hearts subjected to 5 min Ca2+-depletion and 30 min Ca2+-repletion (Ca2+-paradox). The Ca2+-paradox hearts exhibited a dramatic depression in left ventricular developed pressure, a marked elevation in left ventricular end diastolic pressure, and more than a 4-fold increase in TNF-alpha content. The ratio of cytosolic to homogenate nuclear factor-kappaB (NFkappaB) was decreased whereas the ratio of phospho-NFkappaB to total NFkappaB was increased in the Ca2+-paradox hearts. All these changes due to Ca2+-paradox were significantly attenuated upon treating the hearts with 100 microM pentoxifylline. These results suggest that activation of NFkappaB and increased production of TNF-alpha may play an important role in cardiac injury due to intracellular Ca2+-overload.
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