Effect of Training Induces Changes in Heart, CaMKII Dependent or Not?

Abstract

BackgroundActivation of the multifunctional Ca2+/Calmodulin-dependant protein kinase II (CaMKII) is a decisive step in the development of heart failure. Interestingly, increased CaMKII activation was associated with improved cardiomyocyte function after exercise training in healthy mice. Here we determined whether CaMKII inhibition (KN-93) reduce the exercise training response on healthy hearts.Methods18 mice were included; KN-93 exercise, KN-93 sedentary, sham exercise and, sham sedentary. The exercise groups performed high intensity aerobic interval training 5 days a week for six weeks. KN-93 groups had daily intraperitoneal injections of KN-93 while sham were IP injected with DMSO. Ca2+ handling were measured in isolated cardiomyocytes, while in vivo myocardial function was assessed by echocardiography.ResultsVO2max increased with 12 % in KN-93 exercise and 5 % in sham exercise, significant higher compared to sedentary groups (P<0.05). In vivo cardiac function was only improved in sham exercise (P<0.02). Fractional shortening from isolated cardiomyocytes improved in a similar magnitude in both exercise groups. KN-93 treated had reduced diastolic function, reflected by 25% slower re-lengthening than sham. Exercise training decreased time to 50% re-lengthening in KN-93 exercise (P<0.05) and sham exercise (P<0.01) vs. sedentary groups. This was reflected by Ca2+ decay, were both exercise groups reduced time to 50% Ca2+ decay, fastest in sham exercised. Cardiomyocyte hypertrophy occurred in both exercise groups with a significant higher response in the sham exercised compared to the KN-93 exercised (length; 13% vs. 8%, P<0.05, width; 30% vs. 14%, P<0.05, in sham exercised vs. KN-93 exercised, respectively).ConclusionCaMKII inhibition attenuated exercise training response on cardiomyocytes, but lead to higher levels of maximal oxygen uptake.