Hoydal, Morten A. and Stolen, Tomas O. and Kettlewell, Sarah and Maier, Lars S. and Brown, Joan Heller and Sowa, Tomas and Catalucci, Daniele and Condorelli, Gianluigi and Kemi, Ole J. and Smith, Godfrey L. and Wisloff, Ulrik (2016) Exercise training reverses myocardial dysfunction induced by CaMKII delta(C) overexpression by restoring Ca2+ homeostasis. JOURNAL OF APPLIED PHYSIOLOGY, 121 (1). pp. 212-220. ISSN 8750-7587, 1522-1601
Full text not available from this repository. (Request a copy)Abstract
Several conditions of heart disease, including heart failure and diabetic cardiomyopathy, are associated with upregulation of cytosolic Ca2+ /calmodulin-dependent protein kinase II (CaMKII delta(C)) activity. In the heart, CaMKII delta(C) isoform targets several proteins involved in intracellular Ca2+ homeostasis. We hypothesized that high-intensity endurance training activates mechanisms that enable a rescue of dysfunctional cardiomyocyte Ca2+ handling and thereby ameliorate cardiac dysfunction despite continuous and chronic elevated levels of CaMKII delta(C). CaMKII delta(C) transgenic (TG) and wild-type (WT) mice performed aerobic interval exercise training over 6 wk. Cardiac function was measured by echocardiography in vivo, and cardiomyocyte shortening and intracellular Ca2+ handling were measured in vitro. TG mice had reduced global cardiac function, cardiomyocyte shortening (47% reduced compared with WT, P < 0.01), and impaired Ca2+ homeostasis. Despite no change in the chronic elevated levels of CaMKII delta(C), exercise improved global cardiac function, restored cardiomyocyte shortening, and reestablished Ca2+ homeostasis to values not different from WT. The key features to explain restored Ca2+ homeostasis after exercise training were increased L-type Ca2+ current density and flux by 79 and 85%, respectively (P < 0.01), increased sarcoplasmic reticulum (SR) Ca2+ -ATPase (SERCA2a) function by 50% (P < 0.01), and reduced diastolic SR Ca2+ leak by 73% (P < 0.01), compared with sedentary TG mice. In conclusion, exercise training improves global cardiac function as well as cardiomyocyte function in the presence of a maintained high CaMKII activity. The main mechanisms of exercise-induced improvements in TG CaMKII delta(C) mice are mediated via increased L-type Ca2+ channel currents and improved SR Ca2+ handling by restoration of SERCA2a function in addition to reduced diastolic SR Ca2+ leak.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE; HEART-FAILURE; CARDIAC MYOCYTES; CARDIOMYOCYTE CONTRACTILITY; SKELETAL-MUSCLE; CALCIUM LEAK; HYPERTROPHY; INTENSITY; DISEASE; CAMKII; calcium handling; CaM kinase; exercise training; heart disease |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2019 12:44 |
| Last Modified: | 20 Mar 2019 12:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3661 |
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