Malleability of human skeletal muscle sarcoplasmic reticulum to short-term training

2011 ◽  
Vol 36 (6) ◽  
pp. 904-912 ◽  
Author(s):  
Howard J. Green ◽  
Margaret Burnett ◽  
Helen Kollias ◽  
Jing Ouyang ◽  
Ian Smith ◽  
...  

This study investigated the hypothesis that adaptations would occur in the sarcoplasmic reticulum in vastus lateralis soon after the onset of aerobic-based training consistent with reduced Ca2+-cycling potential. Tissue samples were extracted prior to (0 days) and following 3 and 6 days of cycling performed for 2 h at 60%–65% of peak aerobic power (VO2peak) in untrained males (VO2peak = 47 ± 2.3 mL·kg–1·min–1; mean ± SE, n = 6) and assessed for changes (nmol·mg protein–1·min–1) in maximal Ca2+-ATPase activity (Vmax), Ca2+-uptake, and Ca2+-release (phase 1 and phase 2) as well as the sarcoplasmic (endoplasmic) reticulum Ca2+-ATPase (SERCA) isoforms. Training resulted in reductions (p < 0.05) in SERCA1a at 6 days (–14%) but not at 3 days. For SERCA2a, reductions (p < 0.05) were also noted only at 6 days (–7%). For Vmax, depressions (p < 0.05) were found at 6 days (172 ± 11) but not at 3 days (176 ± 13; p < 0.10) compared with 0 days (192 ± 11). These changes were accompanied by a lower (p < 0.05) Ca2+-uptake at both 3 days (–39%) and 6 days (–48%). A similar pattern was found for phase 1 Ca2+-release with reductions (p < 0.05) of 37% observed at 6 days and 23% (p = 0.21) at 3 days of training, respectively. In a related study using the same training protocol and participant characteristics, microphotometric determinations of Vmax indicated reductions (p < 0.05) in type I at 3 days (–27%) and at 6 days (–34%) and in type IIA fibres at 6 days (–17%). It is concluded that in response to aerobic-based training, sarcoplasmic reticulum Ca2+-cycling potential is reduced by adaptations that occur soon after training onset.

2007 ◽  
Vol 103 (4) ◽  
pp. 1212-1220 ◽  
Author(s):  
T. A. Duhamel ◽  
R. D. Stewart ◽  
A. R. Tupling ◽  
J. Ouyang ◽  
H. J. Green

The study investigated the hypothesis that three consecutive days of prolonged cycle exercise would result in a sustained reduction in the Ca2+-cycling properties of the vastus lateralis in the absence of changes in the sarcoplasmic (endoplasmic) reticulum Ca2+-ATPase (SERCA) protein. Tissue samples were obtained at preexercise (Pre) and postexercise (Post) on day 1 (E1) and day 3 (E3) and during recovery day 1 (R1), day 2 (R2), and day 3 (R3) in 12 active but untrained volunteers (age 19.2 ± 0.27 yr; mean ± SE) and analyzed for changes (nmol·mg protein−1·min−1) in maximal Ca2+-ATPase activity ( Vmax), Ca2+ uptake and Ca2+ release (phase 1 and phase 2), and SERCA isoform expression (SERCA1a and SERCA2a). At E1, reductions ( P < 0.05) from Pre to Post in Vmax (150 ± 7 vs. 121 ± 7), Ca2+ uptake (7.79 ± 0.28 vs. 5.71 ± 0.33), and both phases of Ca2+ release (phase 1, 20.3 ± 1.3 vs. 15.2 ± 1.1; phase 2, 7.70 ± 0.60 vs. 4.99 ± 0.48) were found. In contrast to Vmax, which recovered at Pre E3 and then remained stable at Post E3 and throughout recovery, Ca2+ uptake remained depressed ( P < 0.05) at E3 Pre and Post and at R1 as did phase 2 of Ca2+ release. Exercise resulted in an increase ( P < 0.05) in SERCA1a (14% at R2) but not SERCA2a. It is concluded that rapidly adapting mechanisms protect Vmax following the onset of regular exercise but not Ca2+ uptake and Ca2+ release.


2005 ◽  
Vol 99 (3) ◽  
pp. 836-843 ◽  
Author(s):  
G. P. Holloway ◽  
H. J. Green ◽  
T. A. Duhamel ◽  
S. Ferth ◽  
J. W. Moule ◽  
...  

The repetition-dependent effects of a repetitive heavy exercise protocol previously shown to alter muscle mechanic behavior (Green HJ, Duhamel TA, Ferth S, Holloway GP, Thomas MM, Tupling AR, Rich SM, and Yau JE. J Appl Physiol 97: 2166–2175, 2004) on muscle sarcoplasmic reticulum (SR) Ca2+-transport properties, measured in vitro, were examined in 12 untrained volunteers [peak aerobic power (V̇o2 peak) = 44.3 ± 0.66 ml·kg−1·min−1]. The protocol involved 6 min of cycle exercise performed at ∼91% V̇o2 peak once per hour for 16 h. Tissue samples were obtained from the vastus lateralis before (B) and after (A) exercise at repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). Reductions ( P < 0.05) in maximal Ca2+-ATPase activity ( Vmax) of 26 and 12% with exercise were only observed at R1 and R16, respectively. Vmax remained depressed ( P < 0.05) at R2 (B) but not at R9 (B) and R16 (B). No changes were observed in two other kinetic properties of the enzyme, namely the Hill coefficient (defined as the slope of the relationship between Ca2+-ATPase activity and free Ca2+ concentration) and the Ca50 (defined as the free Ca2+ concentration needed to elicit 50% Vmax). Changes in Ca2+ uptake (measured at 2,000 nM) with exercise and recovery generally paralleled Vmax. The apparent coupling ratio, defined as the ratio between Ca2+ uptake and Vmax, was unaffected by the intermittent protocol. Reductions ( P < 0.05) in phase 1 Ca2+ release (32%) were only observed at R1. No differences were observed between B and A for R2, R9, and R16 or between B and B for R1, R2, R9, and R16. The changes in phase 2 Ca2+ release were as observed for phase 1 Ca2+ release. It is concluded that the SR Ca2+-handling properties, in general, display rapid adaptations to repetitive exercise.


2006 ◽  
Vol 291 (4) ◽  
pp. R1100-R1110 ◽  
Author(s):  
T. A. Duhamel ◽  
J. G. Perco ◽  
H. J. Green

The hypothesis tested was that disturbances in the sarcoplasmic reticulum (SR) Ca2+-cycling responses to exercise would associate with muscle glycogen reserves. Ten untrained males [peak O2consumption (V̇o2 peak) = 3.41 ± 0.20 (SE) l/min] performed a standardized cycle test (∼70% V̇o2 peak) on two occasions, namely, following 4 days of a high (Hi CHO)- and 4 days of a low (Lo CHO)-carbohydrate diet. Both Hi CHO and Lo CHO were preceded by a session of prolonged exercise designed to deplete muscle glycogen. SR Ca2+cycling in crude homogenates prepared from vastus lateralis samples indicated higher ( P < 0.05) Ca2+uptake (μM·g protein−1·min−1) in Hi CHO compared with Lo CHO at 30 min (2.93 ± 0.10 vs. 2.23 ± 0.12) and at 67 min (2.77 ± 0.16 vs. 2.10 ± 0.12) of exercise, the point of fatigue in Lo CHO. Similar effects ( P < 0.05) were noted between conditions for maximal Ca2+-ATPase (μM·g protein−1·min−1) at 30 min (142 ± 8.5 vs. 107 ± 5.0) and at 67 min (130 ± 4.5 vs. 101 ± 4.7). Both phase 1 and phase 2 Ca2+release were 23 and 37% higher ( P < 0.05) at 30 min of exercise and 15 and 34% higher ( P < 0.05), at 67 min during Hi CHO compared with Lo CHO, respectively. No differences between conditions were observed at rest for any of these SR properties. Total muscle glycogen (mmol glucosyl units/kg dry wt) was higher ( P < 0.05) in Hi CHO compared with Lo CHO at rest (+36%), 30 min (+53%), and at 67 min (+44%) of cycling. These results indicate that exercise-induced reductions in SR Ca2+-cycling properties occur earlier in exercise during low glycogen states compared with high glycogen states.


Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Nancy R Cook ◽  
Lawrence J Appel ◽  
Paul K Whelton

Introduction: Although weight loss has favorable effects on intermediate outcomes, such as blood pressure and insulin resistance, few studies have examined its effects on long-term outcomes including total mortality. Methods: In the Trials of Hypertension Prevention (TOHP) individuals aged 30-54 years with high normal BP were randomized to a weight loss intervention, to one of several other lifestyle or dietary supplement interventions, or to usual care. All participants from Phase 1 (1987-90) and Phase 2 (1990-5) were followed for mortality through 2013. The association of weight change during any of the interventions with long-term mortality up to 18-24 years after the trial periods was examined among 3828 participants who fell into a high baseline weight stratum, defined as body mass index at least 26 kg/m2 in men and 24 kg/m2 in women. Results and Conclusions: There were 1477 high-weight participants in Phase 1 and 2351 in Phase 2, of whom 21% and 50%, respectively, were assigned to a weight loss intervention. Overall, mean weight change during the trial period was -1.8 lbs (-0.8% of baseline body weight) over 1.5 years in Phase 1 and 1.6 lbs (0.8%) over 3-4 years in Phase 2. A total of 556 (15%) lost > 5%, 1,101 (29%) lost <=5%, 1,567 (41%) gained less than 5%, and 604 (16%) gained > 5% in body weight. Corresponding hazard ratios (HRs) for total mortality were 0.82 (95% confidence interval (CI)=0.57-1.18), 0.94 (95% CI=0.72-1.23), 1.00 (reference), and 1.29 (95% CI=0.92-1.80) (p-trend = 0.046). There was a direct linear relationship with percent change in weight during the trial period and later mortality (HR=1.14 per 5% change, 95% CI=1.02-1.28, p=0.019). This association persisted throughout the course of mortality follow-up (Figure). In these healthy individuals taking part in lifestyle and nutrition supplement trials , short-term weight change was directly associated with mortality about two decades later. These results are consistent with a long-term beneficial effect of presumed intentional weight loss on total mortality.


2006 ◽  
Vol 101 (3) ◽  
pp. 695-706 ◽  
Author(s):  
T. A. Duhamel ◽  
H. J. Green ◽  
J. G. Perco ◽  
J. Ouyang

The effects of exercise and diet on sarcoplasmic reticulum Ca2+-cycling properties in female vastus lateralis muscle were investigated in two groups of women following four different conditions. The conditions were 4 days of a low-carbohydrate (Lo CHO) and glycogen-depleting exercise plus a Lo CHO diet (Ex + Lo CHO) ( experiment 2) and 4 days of normal CHO (Norm CHO) and glycogen-depleting exercise plus Norm CHO (Ex + Norm CHO) ( experiment 1). Peak aerobic power (V̇o2peak) was 38.1 ± 1.4 (SE); n = 9 and 35.6 ± 1.4 ml·kg−1·min−1; n = 9, respectively. Sarcoplasmic reticulum properties measured in vitro in homogenates (μmol·g protein−1·min−1) indicated exercise-induced reductions ( P < 0.05) in maximal Ca2+-ATPase activity (0 > 30, 60 min > fatigue), Ca2+ uptake (0 > 30 > 60 min, fatigue), and Ca2+ release, both phase 1 (0, 30 > 60 min, fatigue) and phase 2 (0 > 30, 60 min, fatigue; 30 min > fatigue) in Norm CHO. Exercise was without effect in altering the Hill slope ( nH), defined as the slope of relationship between Ca2+-ATPase activity and Ca2+ concentration. No differences were observed between Norm CHO and Ex+Norm CHO. Compared with Norm CHO, Lo CHO resulted in a lower ( P < 0.05) Ca2+ uptake, phase 1 Ca2+ release (30 min), and nH. Ex + Lo CHO resulted in a greater ( P < 0.05) Ca2+ uptake and nH compared with Lo CHO. The results demonstrate that Lo CHO alone can disrupt SR Ca2+ cycling and that, with the exception of Ca2+ release, a glycogen-depleting session of exercise before Lo CHO can reverse the effects.


2001 ◽  
Vol 281 (2) ◽  
pp. L318-L325 ◽  
Author(s):  
Michelle Dipp ◽  
Piers C. G. Nye ◽  
A. Mark Evans

The hypoxic constriction of isolated pulmonary vessels is composed of an initial transient phase ( phase 1) followed by a slowly developing increase in tone ( phase 2). We investigated the roles of the endothelium and of intracellular Ca2+ stores in both preconstricted and unpreconstricted intrapulmonary rabbit arteries when challenged with hypoxia (Po 2 16–21 Torr). Removing the endothelium did not affect phase 1, but phase 2 appeared as a steady plateau. Removing extracellular Ca2+ had essentially the same effect as removing the endothelium. Depletion of sarcoplasmic reticulum Ca2+stores with caffeine and ryanodine abolished the hypoxic response. Omitting preconstriction reduced the amplitude of the hypoxic response but did not qualitatively affect any of the above responses. We conclude that hypoxia releases intracellular Ca2+ from ryanodine-sensitive stores by a mechanism intrinsic to pulmonary vascular smooth muscle without the need for Ca2+ influx across the plasmalemma or an endothelial factor. Our results also suggest that extracellular Ca2+ is required for the release of an endothelium-derived vasoconstrictor.


1999 ◽  
Vol 277 (1) ◽  
pp. E39-E48 ◽  
Author(s):  
H. Green ◽  
S. Grant ◽  
E. Bombardier ◽  
D. Ranney

To investigate the hypothesis that training-induced increases in muscle mitochondrial potential are not obligatory to metabolic adaptations observed during submaximal exercise, regardless of peak aerobic power (V˙o 2 peak) of the subjects, a short-term training study was utilized. Two groups of untrained male subjects ( n = 7/group), one with a high (HI) and the other with a low (LO)V˙o 2 peak(means ± SE; 51.4 ± 0.90 vs. 41.0 ± 1.3 ml ⋅ kg−1 ⋅ min−1; P< 0.05), cycled for 2 h/day at 66–69% ofV˙o 2 peak for 6 days. Muscle tissue was extracted from vastus lateralis at 0, 3, and 30 min of standardized cycle exercise before training (0 days) and after 3 and 6 days of training and analyzed for metabolic and enzymatic changes. During exercise after 3 days of training in the combined HI + LO group, higher ( P < 0.05) concentrations (mmol/kg dry wt) of phosphocreatine (40.5 ± 3.4 vs. 52.2 ± 4.2) and lower ( P < 0.05) concentrations of Pi (61.5 ± 4.4 vs. 53.3 ± 4.4), inosine monophosphate (0.520 ± 0.19 vs. 0.151 ± 0.05), and lactate (37.9 ± 5.5 vs. 22.8 ± 4.8) were observed. These changes were also accompanied by reduced levels of calculated free ADP, AMP, and Pi. All adaptations were fully expressed by 3 min of exercise and by 3 days of training and were independent of initialV˙o 2 peak levels. Moreover, maximal activity of citrate synthase, a measure of mitochondrial capacity, was only increased with 6 days of training (5.71 ± 0.29 vs. 7.18 ± 0.37 mol ⋅ kg protein−1 ⋅ h−1; P < 0.05). These results demonstrate that metabolic adaptations to prolonged exercise occur within the first 3 days of training and during the non-steady-state period. Moreover, neither time course nor magnitude of metabolic adaptations appears to depend on increases in mitochondrial potential or on initial aerobic power.


1993 ◽  
Vol 264 (6) ◽  
pp. C1538-C1541 ◽  
Author(s):  
H. J. Green ◽  
E. R. Chin ◽  
M. Ball-Burnett ◽  
D. Ranney

To investigate the effect of short-term training on Na(+)-K(+)-adenosine triphosphatase (ATPase) concentration in skeletal muscle and on plasma K+ homeostasis during exercise, 9 subjects performed cycle exercise for 2 h per day for 6 consecutive days at 65% of maximal aerobic power (VO2 max). Na(+)-K(+)-ATPase concentration determined from biopsies obtained from the vastus lateralis muscle using the [3H]ouabain-binding technique increased 13.6% (P < 0.05) as a result of the training (339 +/- 16 vs. 385 +/- 19 pmol/g wet wt, means +/- SE). Increases in Na(+)-K(+)-ATPase concentration were accompanied by a small but significant increase in VO2 max (3.36 +/- 0.16 vs. 3.58 +/- 0.13 l/min). The increase in arterialized plasma K+ concentration and plasma K+ content determined during continuous exercise at three different intensities (60, 79, and 94% VO2 max) was depressed (P < 0.05) following training. These results indicate that not only is training capable of inducing an upregulation in sarcolemmal Na(+)-K(+)-ATPase concentration in humans, but provided that the exercise is of sufficient intensity and duration, the upregulation can occur within the first week of training. Moreover, our findings are consistent with the notion that the increase in Na(+)-K(+)-ATPase pump concentration attenuates the loss of K+ from the working muscle.


2001 ◽  
Vol 281 (2) ◽  
pp. E224-E232 ◽  
Author(s):  
R. Tupling ◽  
H. Green ◽  
G. Senisterra ◽  
J. Lepock ◽  
N. McKee

In this study, we investigated the hypothesis that prolonged ischemia would impair both sarcoplasmic reticulum (SR) Ca2+ uptake and Ca2+ release in skeletal muscle. To induce total ischemia (I), a tourniquet was placed around the upper hindlimb in 30 female Sprague-Dawley rats [wt = 256 ± 6.7 (SE) g] and inflated to 350 mmHg for 4 h. The contralateral limb served as control (C). Immediately after the 4 h of ischemia, mixed gastrocnemius and tibialis anterior muscle was sampled from both limbs, and both crude muscle homogenates and SR vesicles were prepared. In another 10 control animals (CC), muscles were sampled and prepared exactly the same way, but immediately after anesthetization. Ca2+ uptake and Ca2+ release were measured in vitro with Indo-I on both homogenates and SR vesicles. As hypothesized, submaximal Ca2+ uptake was lower ( P < 0.05) in I compared with CC and C, by 25 and 45% in homogenates and SR vesicles, respectively. Silver nitrate (AgNO3)-induced Ca2+ release, which occurred in two phases ( phase 1 and phase 2), was also altered in I compared with CC and C, in both muscle homogenates and SR vesicles. With ischemia, phase 1 peak Ca2+ release was 26% lower ( P < 0.05) in SR vesicles only. For phase 2, peak Ca2+ release was 54 and 24% lower ( P < 0.05) in SR vesicles and homogenates, respectively. These results demonstrate that prolonged skeletal muscle ischemia leads to a reduced SR Ca2+uptake in both homogenates and SR vesicles. The effects of ischemia on SR Ca2+ release, however, depend on both the phase examined and the type of tissue preparation.


2009 ◽  
Vol 297 (5) ◽  
pp. R1383-R1391 ◽  
Author(s):  
H. J. Green ◽  
E. Bombardier ◽  
M. E. Burnett ◽  
I. C. Smith ◽  
S. M. Tupling ◽  
...  

In this study, we investigated the hypothesis that the metabolic adaptations observed during steady-state exercise soon after the onset of training would be displayed during the nonsteady period of moderate exercise and would occur in the absence of increases in peak aerobic power (V̇o2peak) and in muscle oxidative potential. Nine untrained males [age = 20.8 ± 0.70 (SE) yr] performed a cycle task at 62% V̇o2peak before (Pre-T) and after (Post-T) training for 2 h/day for 5 days at task intensity. Tissue samples extracted from the vastus lateralis at 0 min (before exercise) and at 10, 60, and 180 s of exercise, indicated that at Pre-T, reductions ( P < 0.05) in phosphocreatine and increases ( P < 0.05) in creatine, inorganic phosphate, calculated free ADP, and free AMP occurred at 60 and 180 s but not at 10 s. At Post-T, the concentrations of all metabolites were blunted ( P < 0.05) at 60 s. Training also reduced ( P < 0.05) the increase in lactate and the lactate-to-pyruvate ratio observed during exercise at Pre-T. These adaptations occurred in the absence of change in V̇o2peak (47.8 ± 1.7 vs. 49.2 ± 1.7 ml·kg−1·min−1) and in the activities (mol·kg protein−1·h−1) of succinic dehydrogenase (3.48 ± 0.21 vs. 3.77 ± 0.35) and citrate synthase (7.48 ± 0.61 vs. 8.52 ± 0.65) but not cytochrome oxidase (70.8 ± 5.1 vs. 79.6 ± 6.6 U/g protein; P < 0.05). It is concluded that the tighter metabolic control observed following short-term training is initially expressed during the nonsteady state, probably as a result of increases in oxidative phosphorylation that is not dependent on changes in V̇o2peak while the role of oxidative potential remains uncertain.


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