I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Fiber types in mammalian skeletal muscles.

Repeated, intense use of muscles leads to a decline in performance known as muscle fatigue. Many muscle properties change during fatigue including the action potential, extracellular and intracellular ions, and many intracellular metabolites. A range of mechanisms have been identified that contribute to the decline of performance. The traditional explanation, accumulation of intracellular lactate and hydrogen ions causing impaired function of the contractile proteins, is probably of limited importance in mammals. Alternative explanations that will be considered are the effects of ionic changes on the action potential, failure of SR Ca2+ release by various mechanisms, and the effects of reactive oxygen species. Many different activities lead to fatigue, and an important challenge is to identify the various mechanisms that contribute under different circumstances. Most of the mechanistic studies of fatigue are on isolated animal tissues, and another major challenge is to use the knowledge generated in these studies to identify the mechanisms of fatigue in intact animals and particularly in human diseases.

/pdf/skeletal-muscle-fatigue-cellular-mechanisms-d0dzk4w31g.pdf

Skeletal Muscle Fatigue: Cellular Mechanisms

The molecular origin of standard metabolic rate and thermogenesis in mammals is examined. It is pointed out that there are important differences and distinctions between the cellular reactions that 1) couple to oxygen consumption, 2) uncouple metabolism, 3) hydrolyze ATP, 4) control metabolic rate, 5) regulate metabolic rate, 6) produce heat, and 7) dissipate free energy. The quantitative contribution of different cellular reactions to these processes is assessed in mammals. We estimate that approximately 90% of mammalian oxygen consumption in the standard state is mitochondrial, of which approximately 20% is uncoupled by the mitochondrial proton leak and 80% is coupled to ATP synthesis. The consequences of the significant contribution of proton leak to standard metabolic rate for tissue P-to-O ratio, heat production, and free energy dissipation by oxidative phosphorylation and the estimated contribution of ATP-consuming processes to tissue oxygen consumption rate are discussed. Of the 80% of oxygen consumption coupled to ATP synthesis, approximately 25-30% is used by protein synthesis, 19-28% by the Na(+)-K(+)-ATPase, 4-8% by the Ca2(+)-ATPase, 2-8% by the actinomyosin ATPase, 7-10% by gluconeogenesis, and 3% by ureagenesis, with mRNA synthesis and substrate cycling also making significant contributions. The main cellular reactions that uncouple standard energy metabolism are the Na+, K+, H+, and Ca2+ channels and leaks of cell membranes and protein breakdown. Cellular metabolic rate is controlled by a number of processes including metabolic demand and substrate supply. The differences in standard metabolic rate between animals of different body mass and phylogeny appear to be due to proportionate changes in the whole of energy metabolism. Heat is produced by some reactions and taken up by others but is mainly produced by the reactions of mitochondrial respiration, oxidative phosphorylation, and proton leak on the inner mitochondrial membrane. Free energy is dissipated by all cellular reactions, but the major contributions are by the ATP-utilizing reactions and the uncoupling reactions. The functions and evolutionary significance of standard metabolic rate are discussed.

Cellular energy utilization and molecular origin of standard metabolic rate in mammals

Low-volume ‘sprint’ interval training (SIT) stimulates rapid improvements in muscle oxidative capacity that are comparable to levels reached following traditional endurance training (ET) but no study has examined metabolic adaptations during exercise after these different training strategies. We hypothesized that SIT and ET would induce similar adaptations in markers of skeletal muscle carbohydrate (CHO) and lipid metabolism and metabolic control during exercise despite large differences in training volume and time commitment. Active but untrained subjects (23 ± 1 years) performed a constant-load cycling challenge (1 h at 65% of peak oxygen uptake ( ˙ VO2peak) before and after 6 weeks of either SIT or ET (n = 5 men and 5 women per group). SIT consisted of four to six repeats of a 30 s ‘all out’ Wingate Test (mean power output ∼500 W) with 4.5 min recovery between repeats, 3 days per week. ET consisted of 40‐60 min of continuous cycling at a workload that elicited ∼65% ˙ VO2peak (mean power output ∼150 W) per day, 5 days per week. Weekly time commitment (∼1.5 versus ∼4.5 h) and total training volume (∼225 versus ∼2250 kJ week −1 ) were substantially lower in SIT versus ET. Despite these differences, both protocols induced similar increases (P < 0.05) in mitochondrial markers for skeletal muscle CHO (pyruvate dehydrogenase E1α protein content) and lipid oxidation (3-hydroxyacyl CoA dehydrogenase maximal activity) and protein content of peroxisome proliferator-activated receptor-γ coactivator-1α. Glycogen and phosphocreatine utilization during exercise were reduced after training, and calculated rates of whole-body CHO and lipid oxidation were decreased and increased, respectively, with no differences between groups (all main effects, P < 0.05). Given the markedly lower training volume in the SIT group, these data suggest that high-intensity interval training is a time-efficient strategy to increase skeletal muscle oxidative capacity and induce specific metabolic adaptations during exercise that are comparable to traditional ET.

/pdf/similar-metabolic-adaptations-during-exercise-after-low-2koff0yn94.pdf

Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans

The variability of the triacylglycerol store in human skeletal muscle (TGm) was examined using the needle biopsy technique. In 13 subjects, three biopsies were sampled from the vastus lateralis muscle of one leg at rest and after 90 min of cycling at 65% of maximal O2 uptake on one or two occasions. Visible fat and blood were removed before the samples were frozen, and remaining blood, connective tissue, and fat were removed from freeze-dried fiber bundles. TGm content was measured in two aliquots of powdered muscle from each biopsy. Within-biopsy variability was low at 6%. Despite precautions, many biopsies from inactive subjects were contaminated with adipose tissue. The TGm between-biopsy coefficient of variation (CV) was 23.5 +/- 14.6% (SD, n = 24) for rest and exercise time points where three noncontaminated biopsies existed. The between-biopsy variability at rest (19.8 +/- 7.9%, n = 10) was not significantly different from that at exercise (26.1 +/- 17.4%, n = 14). The muscle glycogen between-biopsy CV for rest and exercise time points was 10.0 +/- 10.3%. The resting TGm content was 26.3 +/- 4.3 mmol/kg dry muscle, and the net utilization during the 90 min of exercise was less than the between-biopsy variability. It is concluded that the TGm store measured in repeated biopsies of human skeletal muscle is variable, with a CV of 20-26%. Therefore, because of this high variability, only changes greater than approximately 24% of resting TGm content may be considered meaningful.

Variability of triacylglycerol content in human skeletal muscle biopsy samples

The adaptation of pulmonary oxygen uptake during the transition to moderate-intensity exercise (Mod) is faster following a prior bout of heavy-intensity exercise In the present study we examined the activation of pyruvate dehydrogenase (PDHa) during Mod both with and without prior heavy-intensity exercise Subjects (n= 9) performed a Mod1–heavy-intensity–Mod2 exercise protocol preceded by 20 W baseline Breath-by-breath kinetics and near-infrared spectroscopy-derived muscle oxygenation were measured continuously, and muscle biopsy samples were taken at specific times during the transition to Mod In Mod1, PDHa increased from baseline (108 ± 02 mmol min−1 (kg wet wt)−1) to 30 s (205 ± 02 mmol min−1 (kg wet wt)−1), with no additional change at 6 min exercise (207 ± 03 mmol min−1 (kg wet wt)−1) In Mod2, PDHa was already elevated at baseline (188 ± 03 mmol min−1 (kg wet wt)−1) and was greater than in Mod1, and did not change at 30 s (196 ± 02 mmol min−1 (kg wet wt)−1) but increased at 6 min exercise (270 ± 03 mmol min−1 (kg wet wt)−1) The time constant of was lower in Mod2 (19 ± 2 s) than Mod1 (24 ± 3 s) Phosphocreatine (PCr) breakdown from baseline to 30 s was greater (P < 005) in Mod1 (136 ± 67 mmol (kg dry wt)−1) than Mod2 (65 ± 62 mmol (kg dry wt)−1) but total PCr breakdown was similar between conditions (Mod1, 148 ± 74 mmol (kg dry wt)−1; Mod2, 201 ± 80 mmol (kg dry wt)−1) Both oxyhaemoglobin and total haemoglobin were elevated prior to and throughout Mod2 compared with Mod1 In conclusion, the greater PDHa at baseline prior to Mod2 compared with Mod1 may have contributed in part to the faster kinetics in Mod2 That oxyhaemoglobin and total haemoglobin were elevated prior to Mod2 suggests that greater muscle perfusion may also have contributed to the observed faster kinetics These findings are consistent with metabolic inertia, via delayed activation of PDH, in part limiting the adaptation of pulmonary and muscle O2 consumption during the normal transition to exercise

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2006.112706

Prior heavy exercise elevates pyruvate dehydrogenase activity and speeds O2 uptake kinetics during subsequent moderate‐intensity exercise in healthy young adults

Evidence indicates that skeletal muscle lipid droplet-associated proteins (PLINs) regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN1 is thoug...

Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction

The metabolism and performance of a perfused rat hindquarter preparation was examined during heavy exercise in three conditions: control (C), metabolic acidosis (MA, decreased bicarbonate concentration), and respiratory acidosis (RA, increased CO2 tension). A one-pass system was used to perfuse the hindquarters for 30 min at rest and 20 min during tetanic stimulation via the sciatic nerve. The isometric tension generated by the gastrocnemius-plantaris-soleus muscle group was recorded, and biopsies were taken pre- and postperfusion. Initial isometric tensions were similar in all conditions, but the rate of tension decay was largest in acidosis; the 5-min tensions for C, MA, and RA were 1,835 +/- 63, 1,534 +/- 63, and 1,434 +/- 73 g, respectively. O2 uptake in C was greater than in MA and RA (23.4 +/- 1.3 vs. 17.0 +/- 1.4 and 16.5 +/- 2.3 mumol X min-1), paralleling the tension findings. Hindquarter lactate release was greatest in C, least in MA, and intermediate in RA. Acidosis resulted in less muscle glycogen utilization and lactate accumulation than during control. Muscle creatine phosphate utilization and ATP levels were unaffected by acidosis. Acidosis decreased the muscle's ability to generate isometric tension and depressed both aerobic and anaerobic metabolism. During stimulation in this model lactate left the muscle mainly as a function of the production rate, although a low plasma bicarbonate concentration at pH 7.15 depressed muscle lactate release.

Effects of acidosis on rat muscle metabolism and performance during heavy exercise

Whole body glucose disposal and skeletal muscle hexokinase, glycogen synthase (GS), pyruvate dehydrogenase (PDH), and PDH kinase (PDK) activities were measured in aerobically trained men after a st...

Sandra J. Peters

Papers

Variability of triacylglycerol content in human skeletal muscle biopsy samples

Prior heavy exercise elevates pyruvate dehydrogenase activity and speeds O2 uptake kinetics during subsequent moderate‐intensity exercise in healthy young adults

Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction

Effects of acidosis on rat muscle metabolism and performance during heavy exercise

Enzymatic regulation of glucose disposal in human skeletal muscle after a high-fat, low-carbohydrate diet