Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats

Wisløff, Ulrik; Loennechen, Jan Pål; Falck, Geir; Beisvåg, Vidar; Currie, Susan; Smith, Godfrey L.; Ellingsen, Øyvind

doi:10.1016/s0008-6363(01)00210-3

Cited by 175 publications

(242 citation statements)

References 38 publications

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“…The cellular basis for this involves improved contractile function of the cardiomyocyte, which we have demonstrated occurs with exercise training in rats [1][2][3]. The present study confirms that these changes occur in cardiomyocytes isolated from exercise trained mice, and identify sub-cellular mechanisms that contribute to improved inotropy and lusitropy.…”

Section: Aerobic Interval Training Up-regulates Serca-2a Plb and Camksupporting

confidence: 82%

“…Since PLB is the primary inhibitor of SERCA-2a [8,16], the reduced ratio will increase the Ca 2+ sensitivity and the enzyme activity (V max ) of SERCA-2a. Increased SERCA-2a mRNA [17] and protein [2] expressions have previously been reported in exercise trained rats. Further increases in the Ca 2+ sensitivity (reduced affinity for Ca 2+ , K m ) of SERCA-2a would result from the increased phosphorylation of the Thr-17 of PLB [16,18], although it has also been suggested that Thr-17 phosphorylation of PLB also may increase the V max of SERCA-2a [19,20].…”

Section: Aerobic Interval Training Up-regulates Serca-2a Plb and Camkmentioning

confidence: 64%

“…We have previously shown that aerobic capacity is closely related to cardiomyocyte contractility and calcium handling in training [1,2], detraining [3], post-infarction heart failure [4] and genetic selection of high versus low exercise capacity [5]. It has also been demonstrated that exercise-induced improvement of contractile function in cardiomyocytes may be linked to increased activity of the cardiac sarcoplasmic reticulum Ca 2+ ATPase 2a (SERCA-2a) both in healthy rats [2,6] and in rats with post-infarction heart failure [4].…”

Section: Introductionmentioning

confidence: 99%

“…It has also been demonstrated that exercise-induced improvement of contractile function in cardiomyocytes may be linked to increased activity of the cardiac sarcoplasmic reticulum Ca 2+ ATPase 2a (SERCA-2a) both in healthy rats [2,6] and in rats with post-infarction heart failure [4]. Uptake of Ca 2+ into sarcoplasmic reticulum (SR) by SERCA-2a is an important determinant of the rate of cardiac muscle relaxation.…”

Section: Introductionmentioning

confidence: 99%

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

Kemi

Ellingsen

Ceci

et al. 2007

Journal of Molecular and Cellular Cardiology

114

116

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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.

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Section: Aerobic Interval Training Up-regulates Serca-2a Plb and Camksupporting

confidence: 82%

Section: Aerobic Interval Training Up-regulates Serca-2a Plb and Camkmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Kemi

Ellingsen

Ceci

et al. 2007

Journal of Molecular and Cellular Cardiology

114

116

View full text Add to dashboard Cite

show abstract

“…In brief, at 6 weeks of age, rats in the exercise group exercised daily on a rodent treadmill (Columbus Instruments, Columbus, OH) following a modified training program which comprised a 3-wk progressive intensity-increasing period followed by a 3-wk maintenance period [13,14]. Animals exercised at the running speed of 20 m/min at a 5° incline for 90 min per session in the maintenance period.…”

Section: Induction Of Physiologic Cardiac Hypertrophy and Heart Failurementioning

confidence: 99%

Response of caspase-independent apoptotic factors to high salt diet-induced heart failure

Siu

Bae

Bodyak

et al. 2007

Journal of Molecular and Cellular Cardiology

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The role of caspase-independent apoptotic events in heart failure is largely unknown. The present study examined the response of apoptotic factors, which can function independently of caspase machinery including AIF, EndoG, and HtrA2/Omi to high salt diet-induced pathologic heart failure and exercise-induced physiologic cardiac hypertrophy. Following ~4 months of a daily diet containing 6% salt, animals developed clinical evidence of heart failure accompanied by changes in AIF, EndoG, and HtrA2/Omi. Assessment of the mitochondria-free cytosolic fraction revealed cytosolic accumulations of AIF and processed HtrA2/Omi in the failed ventricle muscles. The subcellular translocation of AIF from mitochondria to cytosol and nuclei was supported by immunofluorescent analysis using confocal microscopy. However, according to our RT-PCR analyses, AIF and EndoG mRNA were decreased, rather than elevated, in the failed heart relative to control heart. No difference in any of the measured parameters of AIF, EndoG, and HtrA2/Omi was found in the ventricle muscle of either exercise-trained or 6 weeks high salt diet fed animals compared to controls. These findings are consistent with the hypothesis that caspase-independent events are involved in cardiac apoptosis during the late remodeling stage of pathologic heart failure.

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Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity

Costa,

Ghouri,

Johnston

et al. 2023

Cell Biochemistry & Function

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Cardiac cellular responses to acute exercise remain undescribed. We present a model for mimicking acute aerobic endurance exercise to freshly isolated cardiomyocytes by evoking exercise‐like contractions over prolonged periods of time with trains of electrical twitch stimulations. We then investigated immediate contractile, Ca2+, and metabolic responses to acute exercise in perfused freshly isolated left ventricular rat cardiomyocytes, after a matrix‐design optimized protocol and induced a mimic for acute aerobic endurance exercise by trains of prolonged field twitch stimulations. Acute exercise decreased cardiomyocyte fractional shortening 50%–80% (p < .01). This was not explained by changes to intracellular Ca2+ handling (p > .05); rather, we observed a weak insignificant Ca2+ transient increase (p = .11), while myofilament Ca2+ sensitivity increased 20%–70% (p < .05). Acidic pH 6.8 decreased fractional shortening 20%–70% (p < .05) because of 20%–30% decreased Ca2+ transients (p < .05), but no difference occurred between control and acute exercise (p > .05). Addition of 1 or 10 mM La− increased fractional shortening in control (1 mM La−: no difference, p > .05; 10 mM La−: 20%–30%, p < .05) and acute exercise (1 mM La−: 40%–90%, p < .01; 10 mM La−: 50%–100%, p < .01) and rendered acute exercise indifferent from control (p > .05). Intrinsic autofluorescence showed a resting NADstate of 0.59 ± 0.04 and FADstate of 0.17 ± 0.03, while acute exercise decreased NADH/FAD ratio 8% (p < .01), indicating intracellular oxidation. In conclusion, we show a novel approach for studying immediate acute cardiomyocyte responses to aerobic endurance exercise. We find that acute exercise in cardiomyocytes decreases contraction, but Ca2+ handling and myofilament Ca2+ sensitivity compensate for this, while acidosis and reduced energy substrate and mitochondrial ATP generation explain this.

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Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats

Cited by 175 publications

References 38 publications

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

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

Response of caspase-independent apoptotic factors to high salt diet-induced heart failure

Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity

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