Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban

Abstract

Cardiac adaptation to aerobic exercise training includes improved cardiomyocyte contractility and calcium handling. Our objective was to determine whether cytosolic calcium/calmodulindependent kinase II and its downstream targets are modulated by exercise training. A six-week aerobic interval training program by treadmill running increased maximal oxygen uptake by 35% in adult mice, whereupon left ventricular cardiomyocyte function was studied and myocardial tissue samples were used for biochemical analysis. Cardiomyocytes from trained mice had enhanced contractility and faster relaxation rates, which coincided with larger amplitude and faster decay of the calcium transient, but not increased peak systolic calcium levels. These changes were associated with reduced phospholamban expression relative to sarcoplasmic reticulum calcium ATPase, and constitutively increased phosphorylation of phospholamban at the threonine 17, but not at the serine 16 site. Calcium-calmodulin-dependent kinase IIδ phosphorylation was increased at Threonine 287, indicating activation. To investigate the physiological role of calcium/ calmodulin-dependent kinase IIδ phosphorylation, this kinase was blocked specifically by autocamtide-2 related inhibitory peptide II. This maneuver completely abolished training-induced improvements of cardiomyocyte contractility and calcium handling, and blunted, but did not completely abolish the training-induced increase in Ca 2+ sensitivity. Also, inhibition of calcium/ calmodulin-dependent kinase II reduced the greater frequency-dependent acceleration of relaxation that was observed after aerobic interval training. These observations indicate that calcium/calmodulin-dependent kinase IIδ contributes significantly to the functional adaptation of the cardiomyocyte to regular exercise training.

Tropomyosin Dephosphorylation Results in Compensated Cardiac Hypertrophy

“…NTG, n ϭ 3; TG, n ϭ 3. *, indicates p Ͻ 0.05; **, indicates p Ͻ 0.01. phosphorylation are seen (53,54). This is similar to the results found with the ␣-Tm S283A mice.…”

Exercício e restrição alimentar aumentam o RNAm de proteínas do trânsito de Ca2+ miocárdico em ratos

“…When FR was associated with physical training there was a proportional increase of SERCA2a and PLB, indicating that exercise training protected the myocardium from damage caused by the FR. The improvement in the process of reuptake of calcium by the SR induced by physical training is consistent with studies by Kemi et al 32 who reported an increase in the reuptake of calcium in the myocardium derived from the increase of SERCA2a and phosphorylated phospholamban (PLB-thr17) in trained rats. The increased L-channel observed in EX 50 animals suggests an increased influx of calcium to improve the contractile response.…”

Training in the fasted state facilitates re-activation of eEF2 activity during recovery from endurance exercise

“…2). By analogy, Kemi et al (2007) found higher PLN 17 phosphorylation in mouse cardiac muscle after 6 weeks of training, which supports the conclusion that endurance training upregulates basal CaMKII activity in muscle cells. Still, training must probably be maintained for a sufficiently long period because training interventions of less than 3 weeks have been found ineffective to elevate baseline PLN 17 phosphorylation in muscles (Benziane et al 2008;Rose et al 2007).…”

“…For example, consistent exercise training upregulates AMPKa phosphorylation status in human muscle (Frosig et al 2004;Lee-Young et al 2009;Benziane et al 2008), whilst exercise-induced activation of AMPK is downregulated (McConell et al 2005;McConell et al 2008;Lee-Young et al 2009;Benziane et al 2008). Furthermore, after 6 weeks of aerobic training in mice, cardiomyocytes displayed elevated PLN 17 phosphorylation in conjunction with increased CaMKII phosphorylation at Thr 287 (Kemi et al 2007). Rose et al (2007) also previously reported that short-term endurance training elevated CaMKII activity, as well as CaMKII kinase phosphorylation at Thr 287 .…”