Aerobic interval exercise training improved global cardiac function and restored Ca2+ homeostasis in CaMKIIδC transgenic mice by increasing L-type Ca2+ currents and SERCA2a function.
Does aerobic interval exercise training improve myocardial dysfunction and restore Ca2+ homeostasis in CaMKIIδC transgenic mice?
Aerobic interval exercise training reverses myocardial dysfunction and restores calcium homeostasis in a mouse model of CaMKIIδC overexpression, providing a mechanistic basis for the benefits of exercise in heart failure.
p-value: p=<0.01
Several conditions of heart disease, including heart failure and diabetic cardiomyopathy, are associated with upregulation of cytosolic Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIδC) activity. In the heart, CaMKIIδC isoform targets several proteins involved in intracellular Ca(2+) homeostasis. We hypothesized that high-intensity endurance training activates mechanisms that enable a rescue of dysfunctional cardiomyocyte Ca(2+) handling and thereby ameliorate cardiac dysfunction despite continuous and chronic elevated levels of CaMKIIδC CaMKIIδC 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 Ca(2+) handling were measured in vitro. TG mice had reduced global cardiac function, cardiomyocyte shortening (47% reduced compared with WT, P < 0.01), and impaired Ca(2+) homeostasis. Despite no change in the chronic elevated levels of CaMKIIδC, exercise improved global cardiac function, restored cardiomyocyte shortening, and reestablished Ca(2+) homeostasis to values not different from WT. The key features to explain restored Ca(2+) homeostasis after exercise training were increased L-type Ca(2+) current density and flux by 79 and 85%, respectively (P < 0.01), increased sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) function by 50% (P < 0.01), and reduced diastolic SR Ca(2+) 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 CaMKIIδC mice are mediated via increased L-type Ca(2+) channel currents and improved SR Ca(2+) handling by restoration of SERCA2a function in addition to reduced diastolic SR Ca(2+) leak.
Høydal et al. (Thu,) conducted a other in CaMKIIδC overexpression (heart disease model). Aerobic interval exercise training vs. Sedentary TG mice was evaluated on Global cardiac function, cardiomyocyte shortening, and intracellular Ca2+ handling (p=<0.01). Aerobic interval exercise training improved global cardiac function and restored Ca2+ homeostasis in CaMKIIδC transgenic mice by increasing L-type Ca2+ currents and SERCA2a function.
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