J. Ouyang

Regulation of fiber size, oxidative potential, and capillarization in human muscle by resistance exercise

To examine the hypothesis that increases in fiber cross-sectional area mediated by high-resistance training (HRT) would result in a decrease in fiber capillarization and oxidative potential, regardless of fiber type, we studied six untrained males (maximum oxygen consumption, 45.6 +/- 2.3 ml. kg-1. min-1; mean +/- SE) participating in a 12-wk program designed to produce a progressive hypertrophy of the quadriceps muscle. The training sessions, which were conducted 3 times/wk, consisted of three sets of three exercises, each performed for 6-8 repetitions maximum (RM). Measurements of fiber-type distribution obtained from tissue extracted from the vastus lateralis at 0, 4, 7, and 12 wk indicated reductions (P < 0.05) in type IIB fibers (15.1 +/- 2.1% vs. 7.2 +/- 1.3%) by 4 wk in the absence of changes in the other fiber types (types I, IIA, and IIAB). Training culminated in a 17% increase (P < 0.05) in cross-sectional area by 12 wk with initial increases observed at 4 wk. The increase was independent of fiber type-specific changes. The number of capillaries in contact with each fiber type increased by 12 wk, whereas capillary contacts-to-fiber area ratios remained unchanged. In a defined cross-sectional field, HRT also increased the capillaries per fiber at 12 wk. Training failed to alter cellular oxidative potential, as measured by succinic dehydrogenase (SDH) activity, regardless of fiber type and training duration. It is concluded that modest hypertrophy induced by HRT does not compromise cellular tissue capillarization and oxidative potential regardless of fiber type.To examine the hypothesis that increases in fiber cross-sectional area mediated by high-resistance training (HRT) would result in a decrease in fiber capillarization and oxidative potential, regardless of fiber type, we studied six untrained males (maximum oxygen consumption, 45.6 ± 2.3 ml ⋅ kg-1 ⋅ min-1; mean ± SE) participating in a 12-wk program designed to produce a progressive hypertrophy of the quadriceps muscle. The training sessions, which were conducted 3 times/wk, consisted of three sets of three exercises, each performed for 6-8 repetitions maximum (RM). Measurements of fiber-type distribution obtained from tissue extracted from the vastus lateralis at 0, 4, 7, and 12 wk indicated reductions ( P < 0.05) in type IIB fibers (15.1 ± 2.1% vs. 7.2 ± 1.3%) by 4 wk in the absence of changes in the other fiber types (types I, IIA, and IIAB). Training culminated in a 17% increase ( P < 0.05) in cross-sectional area by 12 wk with initial increases observed at 4 wk. The increase was independent of fiber type-specific changes. The number of capillaries in contact with each fiber type increased by 12 wk, whereas capillary contacts-to-fiber area ratios remained unchanged. In a defined cross-sectional field, HRT also increased the capillaries per fiber at 12 wk. Training failed to alter cellular oxidative potential, as measured by succinic dehydrogenase (SDH) activity, regardless of fiber type and training duration. It is concluded that modest hypertrophy induced by HRT does not compromise cellular tissue capillarization and oxidative potential regardless of fiber type.

Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease

To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV(1)) = 42 +/- 6.0% (mean +/- SE)], tissue was extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with that of 12 healthy control subjects (FEV(1) = 114 +/- 3.4%). Compared with controls, lower (P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 +/- 0.65 vs. 17.8 +/- 0.69) and phosphocreatine (81.3 +/- 2.3 vs. 69.1 +/- 4.2) were observed in COPD, which occurred in the absence of differences in the total adenine nucleotide and total creatine pools. Higher concentrations were observed in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was not affected by the disease (289 +/- 20 vs. 269 +/- 20 mmol glucosyl units/kg dry wt). Although no difference between groups was observed for the glucose transporter GLUT1, GLUT4 was reduced by 28% in COPD. For the monocarboxylate transporters, MCT4 was 35% lower in COPD, with no differences observed for MCT1. These results indicate that in resting VL, moderate to severe COPD results in a reduction in phosphorylation potential, an apparent elevation of glycolytic flux rate, and a potential defect in glucose and lactate transport as a result of reduced levels of the principal isoforms.

Metabolic, enzymatic, and transporter responses in human muscle during three consecutive days of exercise and recovery

This study investigated the responses in substrate- and energy-based properties to repetitive days of prolonged submaximal exercise and recovery. Twelve untrained volunteers (Vo(2)(peak) = 44.8 +/- 2.0 ml.kg(-1).min(-1), mean +/- SE) cycled ( approximately 60 Vo(2)(peak)) on three consecutive days followed by 3 days of recovery. Tissue samples were extracted from the vastus lateralis both pre- and postexercise on day 1 (E1), day 3 (E3), and during recovery (R1, R2, R3) and were analyzed for changes in metabolism, substrate, and enzymatic and transporter responses. For the metabolic properties (mmol/kg(-1) dry wt), exercise on E1 resulted in reductions (P < 0.05) in phosphocreatine (PCr; 80 +/- 1.9 vs. 41.2 +/- 3.0) and increases (P < 0.05) in inosine monophosphate (IMP; 0.13 +/- 0.01 vs. 0.61 +/- 0.2) and lactate (3.1 +/- 0.4 vs. 19.2 +/- 4.3). At E3, both IMP and lactate were lower (P < 0.05) during exercise. For the transporters, the experimental protocol resulted in a decrease (P < 0.05) in glucose transporter-1 (GLUT1; 29% by R1), an increase in GLUT4 (29% by E3), and increases (P < 0.05) for both monocarboxylate transporters (MCT) (for MCT1, 23% by R2 and for MCT4, 18% by R1). Of the mitochondrial and cytosolic enzyme activities examined, cytochrome c oxidase (COX), and hexokinase were both reduced (P < 0.05) by exercise at E1 and in the case of hexokinase and phosphorylase by exercise on E3. With the exception at COX, which was lower (P < 0.05) at R1, no differences in enzyme activities existed at rest between E, E3, and recovery days. Results suggest that the glucose and lactate transporters are among the earliest adaptive responses of substrate and metabolic properties studied to the sudden onset of regular low-intensity exercise.

Abnormal sarcoplasmic reticulum Ca2+-sequestering properties in skeletal muscle in chronic obstructive pulmonary disease

The objective of this study was to investigate the hypothesis that alterations in sarcoplasmic reticulum (SR) Ca(2+)-cycling properties would occur in skeletal muscle in patients with moderate to severe chronic obstructive pulmonary disease (COPD). To investigate this hypothesis, tissue samples were obtained from the vastus lateralis of 8 patients with COPD [age 65.6 +/- 3.2 yr; forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) = 44 +/- 2%; mean +/- SE] and 10 healthy age-matched controls (CON, age 67.5 +/- 2.5 yr; FEV(1)/FVC = 77 +/- 2%), and homogenates were analyzed for a wide range of SR properties. Compared with CON, COPD displayed (in mumol.g protein(-1).min(-1)) a 16% lower maximal Ca(2+)-ATPase activity [maximal velocity (V(max)), 158 +/- 10 vs. 133 +/- 7, P < 0.05] and a 17% lower Ca(2+) uptake (4.65 +/- 0.039 vs. 3.85 +/- 0.26, P < 0.05) that occurred in the absence of differences in Ca(2+) release. The lower V(max) in COPD was also accompanied by an 11% lower (P < 0.05) Ca(2+) sensitivity, as measured by the Hill coefficient (defined as the relationship between Ca(2+)-ATPase activity and free cytosolic Ca(2+) concentration for 10-90% V(max)). For the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) isoforms, SERCA1a was 16% higher (P < 0.05) and SERCA2a was 14% lower (P < 0.05) in COPD. It is concluded that moderate to severe COPD results in abnormalities in SR Ca(2+)-ATPase properties that cannot be explained by changes in the SERCA isoform phenotypes. The reduced catalytic properties of SERCA in COPD suggest a disturbance in Ca(2+) cycling, possibly resulting in impairment in Ca(2+)-mediated mechanical function and/or second messenger regulated processes.

Dissociation between changes in muscle Na+-K+-ATPase isoform abundance and activity with consecutive days of exercise and recovery

The early plasticity of vastus lateralis Na(+)-K(+)-ATPase to the abrupt onset of prolonged submaximal cycling was studied in 12 untrained participants (Vo(2 peak) 44.8 +/- 2.0 ml x kg(-1) x min(-1), mean +/- SE) using a 6-day protocol (3 days of exercise plus 3 days of recovery). Tissue samples were extracted prior to (Pre) and following exercise (Post) on day 1 (E1) and day 3 (E3) and on each day of recovery (R1, R2, R3) and analyzed for changes in maximal protein (beta(max)) (vanadate-facilitated [(3)H]ouabain binding), alpha- and beta-isoform concentration (quantitative immunoblotting) and maximal Na(+)-K(+)-ATPase activity (V(max)) (3-O-methylfluorescein K(+)-stimulated phosphatase assay). For beta(max) (pmol/g wet wt), an increase (P < 0.05) of 11.8% was observed at R1 compared with E1-Pre (340 +/- 14 vs 304 +/- 17). For the alpha-isoforms alpha(1), alpha(2), and alpha(3), increases (P < 0.05) of 46, 42, and 31% were observed at R1, respectively. For the beta-isoform, beta(1) and beta(2) increased (P < 0.05) by 19 and 28% at R1, whereas beta(3) increased (P < 0.05) by 18% at R2. With the exception of alpha(2) and alpha(3), the increases in the isoforms persisted at R3. Exercise resulted in an average decrease (P < 0.05) in V(max) by 14.3%. No differences were observed in V(max) at E1 - Pre and E3 - Pre or between R1, R2, and R3. It is concluded that 3 days of prolonged exercise is a powerful stimulus for the rapid upregulation of the Na(+)-K(+)-ATPase subunit isoforms. Contrary to our hypothesis, the increase in subunit expression is not accompanied by increases in the maximal catalytic activity.

Acute responses in muscle mitochondrial and cytosolic enzyme activities during heavy intermittent exercise

To examine the effects of repetitive bouts of heavy exercise on the maximal activities of enzymes representative of the major metabolic pathways and segments, 13 untrained volunteers [peak aerobic power (Vo(2 peak)) = 44.3 +/- 2.3 ml.kg(-1).min(-1)] cycled at approximately 91% Vo(2 peak) for 6 min once per hour for 16 h. Maximal enzyme activities (V(max), mol.kg(-1).protein.h(-1)) were measured in homogenates from tissue extracted from the vastus lateralis before and after exercise at repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). For the mitochondrial enzymes, exercise resulted in reductions (P < 0.05) in cytochrome-c oxidase (COX, 14.6%), near significant reductions in malate dehydrogenase (4.06%; P = 0.06) and succinic dehydrogenase (4.82%; P = 0.09), near significant increases in beta-hydroxyacyl-CoA dehydrogenase (4.94%; P = 0.08), and no change in citrate synthase (CS, 2.88%; P = 0.37). For the cytosolic enzymes, exercise reduced (P < 0.05) V(max) in hexokinase (Hex, 4.4%), creatine phosphokinase (9.0%), total phosphorylase (13.5%), phosphofructokinase (16.6%), pyruvate kinase (PK, 14.1%) and lactate dehydrogenase (10.7%). Repetition-dependent reductions (P < 0.05) in V(max) were observed for CS (R1, R2 > R16), COX (R1, R2 > R16), Hex (1R, 2R > R16), and PK (R9 > R16). It is concluded that heavy exercise results in transient reductions in a wide range of enzymes involved in different metabolic functions and that in the case of selected enzymes, multiple repetitions of the exercise reduce average V(max).

Effects of a 21-Day Expedition to 6194 m on Human Skeletal Muscle SR Ca2+-ATPase

We investigated the effects of a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m) on selected Ca2+ sequestration properties of sarcoplasmic reticulum (SR) calcium pump in vastus lateralis muscle. Muscle samples were obtained by biopsy from 5 male climbers (peak oxygen consumption, VO2peak = 52.3 +/- 2.1 mL.kg(-1).min(-1)) approximately 7 days prior to (PRE) and 4 days following (POST) the expedition. A comparison of PRE versus POST measures of maximal Ca2+-ATPase activities (117 +/- 8.5 vs. 97.6 +/- 5.6 nmol.mg protein(-1).min(-1)) and Ca2+-uptake (204 +/- 15 vs. 161 +/- 11 nmol.mg protein(-1).min(-1)) measured in crude homogenates obtained from pre-exercised muscle, indicated only an effect (p < 0.05) of the expedition on Ca2+-uptake. The reduction in Ca2+-ATPase activity, representing 16.6%, was not significant (p = 0.089). The sarco endoplasmic reticulum calcium (SERCA)-ATPase isoforms, measured using Western blotting techniques, revealed a small reduction (p < 0.05) in SERCA 1 (-4.6 +/- 1.9%), but not in SERCA 2a (+2.0 +/- 1.4%). Prior to the expedition, both Ca2+-ATPase activity and Ca2+-uptake were reduced (p < 0.05) by approximately 34 and 18%, respectively, following 40 min of a two-step continuous cycling task (20 min at 59% VO2peak and 20 min at 74% VO2peak). The exercise-induced reduction in Ca2+-ATPase activity was independent of fiber type. Only in the case of Ca2+-uptake was a lower exercise response (p < 0.05) observed following the expedition, an effect that was due to the lower resting value. It is concluded that acclimatization as experienced during a mountaineering expedition induces changes in the properties of the SR Ca2+-pump, and particularly to Ca2+-sequestering function.

Muscle fatigue and excitation-contraction coupling responses following a session of prolonged cycling.

Aim:  The mechanisms underlying the fatigue that occurs in human muscle following sustained activity are thought to reside in one or more of the excitation–contraction coupling (E–C coupling) processes. This study investigated the association between the changes in select E–C coupling properties and the impairment in force generation that occurs with prolonged cycling.

Muscle metabolic responses during 16 hours of intermittent heavy exercise.

The alterations in muscle metabolism were investigated in response to repeated sessions of heavy intermittent exercise performed over 16 h. Tissue samples were extracted from the vastus lateralis muscle before (B) and after (A) 6 min of cycling at approximately 91% peak aerobic power at repetitions one (R1), two (R2), nine (R9), and sixteen (R16) in 13 untrained volunteers (peak aerobic power = 44.3 +/- 0.66 mL.kg-1.min-1, mean +/- SE). Metabolite content (mmol.(kg dry mass)-1) in homogenates at R1 indicated decreases (p < 0.05) in ATP (21.9 +/- 0.62 vs. 17.7 +/- 0.68) and phosphocreatine (80.3 +/- 2.0 vs. 8.56 +/- 1.5) and increases (p < 0.05) in inosine monophosphate (IMP, 0.077 +/- 0.12 vs. 3.63 +/- 0.85) and lactate (3.80 +/- 0.57 vs. 84.6 +/- 10.3). The content (micromol.(kg dry mass)-1) of calculated free ADP ([ADPf], 86.4 +/- 5.5 vs. 1014 +/- 237) and free AMP ([AMPf], 0.32 +/- 0.03 vs. 78.4 +/- 31) also increased (p < 0.05). No differences were observed between R1 and R2. By R9 and continuing to R16, pronounced reductions (p < 0.05) at A were observed in IMP (72.2%), [ADPf] (58.7%), [AMPf] (85.5%), and lactate (41.3%). The 16-hour protocol resulted in an 89.7% depletion (p < 0.05) of muscle glycogen. Repetition-dependent increases were also observed in oxygen consumption during exercise. It is concluded that repetitive heavy exercise results in less of a disturbance in phosphorylation potential, possibly as a result of increased mitochondrial respiration during the rest-to-work non-steady-state transition.

Cellular properties of extensor carpi radialis brevis and trapezius muscles in healthy males and females

In this study, we sought to determine whether differences in cellular properties associated with energy homeostasis could explain the higher incidence of work-related myalgia in trapezius (TRAP) compared with extensor carpi radialis brevis (ECRB). Tissue samples were obtained from the ECRB (n = 19) and TRAP (n = 17) of healthy males and females (age 27.9 ± 2.2 and 28.1 ± 1.5 years, respectively; mean ± SE) and analyzed for properties involved in both ATP supply and utilization. The concentration of ATP and the maximal activities of creatine phosphokinase, phosphorylase, and phosphofructokinase were higher (P < 0.05) in ECRB than TRAP. Succinic dehydrogenase, citrate synthase, and cytochrome c oxidase were not different between muscles. The ECRB also displayed a higher concentration of Na(+)-K(+)-ATPase and greater sarcoplasmic reticulum Ca(2+) release and uptake. No differences existed between muscles for either monocarboxylate transporters or glucose transporters. It is concluded that the potentials for high-energy phosphate transfer, glycogenolysis, glycolysis, and excitation-contraction coupling are higher in ECRB than TRAP. Histochemical measurements indicated that the muscle differences are, in part, related to differing amounts of type II tissue. Depending on the task demands, the TRAP may experience a greater metabolic and excitation-contraction coupling strain than the ECRB given the differences observed.