Control of adenine nucleotide metabolism and glycolysis in vertebrate skeletal muscle during exercise

The turnover of adenosine triphosphate (ATP) in vertebrate skeletal muscle can increase more than a hundredfold during high-intensity exercise while the content of ATP in muscle may remain virtually unchanged. This requires that the rates of ATP hydrolysis and ATP synthesis are exactly balanced despite large fluctuations in reaction rates. ATP is regenerated initially at the expense of phosphocreatine (PCr) and then mainly through glycolysis from muscle glycogen. The increased ATP turnover in contracting muscle will cause an increase in the contents of adenosine diphosphate (ADP), adenosine monophosphate (AMP) and inorganic phosphate (P_i), metabolites that are substrates and activators of regulatory enzymes such as glycogen phosphorylase and phosphofructokinase. An intracellular metabolic feedback mechanism is thus activated by muscle contraction. How muscle metabolism is integrated in the intact body under physiological conditions is not fully understood. Common frogs are suitable experimental animals for the study of this problem because they can readily be induced to change from rest to high-intensity exercise, in the form of swimming. The changes in metabolites and effectors in gastrocnemius muscle were followed during exercise, post-exercise recovery and repeated exercise. The results suggest that glycolytic flux in muscle is modulated by signals from outside the muscle and that fructose 2,6-bisphosphate is a key signal in this process.     

The effect of exercise on protein turnover in isolated soleus and extensor digitorium longus muscles

Summary The rate of protein degradation was found to be increased in isolated soleus and extensor digitorum muscles of 60–80 g rats after exercise consisting of running for 120 min. These findings support the hypothesis that exercise causes an increase in skeletal muscle protein degradation, and that both red and white muscles are affected similarly.     

Flying insects: model systems in exercise physiology

Insect flight is the most energy-demanding exercise known. It requires very effective coupling of adenosine triphosphate (ATP) hydrolysis and regeneration in the working flight muscles.³¹P nuclear magnetic resonance (NMR) spectroscopy of locust flight muscle in vivo has shown that flight causes only a small decrease in the content of ATP, whereas the free concentrations of inorganic phosphate (P _i ), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were estimated to increase by about 3-, 5- and 27-fold, respectively. These metabolites are potent activators of glycogen phosphorylase and phosphofructokinase (PFK). Activation of glycolysis by AMP and P _i is reinforced synergistically by fructose 2,6-bisphosphate (F2,6P₂), a very potent activator of PFK. During prolonged flight locusts gradually change from using carbohydrate to lipids as their main fuel. This requires a decrease in glycolytic flux which is brought about, at least in part, by a marked decrease in the content of F2,6P₂ in flight muscle (by 80% within 15 min of flight). The synthesis of F2,6P₂ in flight muscle can be stimulated by the nervous system via the biogenic amine octopamine. Octopamine and F2,6P₂ seem to be part of a mechanism to control the rate of carbohydrate oxidation in flight muscle and thus function in the metabolic integration of insect flight.Dedicated to Dr. Ernst Zebe, Emeritus Professor of Zoology (University of Münster) on the occasion of his 70th birthday.     

Leukocyte trafficking in response to magnetic resonance imaging

There were significant increases in total T cells and in T helper cells in blood samples collected immediately following magnetic resonance imaging (MRI) examinations of brains of male volunteers and patients. Percentages of total lymphocytes and suppressor/cytotoxic T cells decreased in these same samples. There were no significant changes in any leukocyte subpopulations in males undergoing lumbar MRI and females undergoing brain MRI. Thus, it is unlikely that stress from the procedure is the explanation for these changes. Our results show that MRI has specific effects on a brain system(s) that controls lymphocyte subpopulations.     

The effect of exercise on protein turnover in isolated soleus and extensor digitorum longus muscles

The rate of protein degradation was found to be increased in isolated soleus and extensor digitorum muscles of 60-80 g rats after exercise consisting of running for 120 min. These findings support the hypothesis that exercise causes an increase in skeletal muscle protein degradation, and that both red and white muscles are affected similarly.     

Two-tiered hypotheses for Duchenne muscular dystrophy

New approaches to understanding and designing treatments for Duchenne muscular dystrophy (DMD) may emerge from two hypotheses outlined here. The proposal that growing skeletal muscle is more susceptible to necrosis than adult muscle raises the possibility that less intensive treatments may be sufficient to protect muscles during the adult phase. The second proposal is that a different balance of cell and molecular events contributes to acute necrosis (e.g. resulting from exercise) compared with chronic damage of dystrophic muscle. Validation of such differences presents the potential for more specific targeting of drugs or nutritional interventions to events downstream of the dystrophin deficiency. A deeper understanding of the events arising as an early consequence of dystrophin deficiency in these two situations may strengthen approaches to therapy for DMD designed to improve muscle function and the quality of life. Received 18 December 2007; received after revision 9 January 2008; accepted 25 February 2008     

Concept of an extracellular regulation of muscular metabolic rate during heavy exercise in humans by psychophysiological feedback

Efferent motor signals to skeletal muscles concern not only the space/time pattern of motion, but also the setting of muscular performance and through this the control of the current metabolic rate. For an optimal adjustment of metabolic rate during heavy exercise — e.g. in athletic competitions — a feedback control system must exist, including a programmer that takes into consideration a finishing point (teleoanticipation). The presented experiments, using Borg's scale, indicate the existence and functioning of a system for optimal adjustment of performance during heavy exercise and the relevance of teleoanticipatory effects. Thus motor learning includes not only somatosensory control, but also metabolic control. With regard to migratory birds, such metabolic control would have to operate in the individual as well as in the migrating flock as a whole.     

Magnetic resonance microscopy: in vivo sectioning of a developing insect

The utility of magnetic resonance imaging vis-a-vis insect morphology and development was investigated. MRI is a noninvasive technique that distinguishes between tissues based on proton content and proton 'environment'. At present a resolution of 100 micron is achievable. The technique avoids fixation artifacts and allows the detection of motion within the organism.     

A review of the electrophysiological,pharmacological and single channel properties of heart ventricle muscle cells in the snailLymnaea stagnalis

Although a considerable body of information has accumulated describing the pharmacological properties of a wide range of molluscan muscle types, the physiological bases underlying these properties have not been thoroughly investigated. At present, little is known about the types of ion channels and their regulation in molluscan muscle cell membranes. Voltage-clamp, and more recently, patch-clamp techniques have revealed molluscan muscles possess a complex array of channel types with various pharmacological and electrophysiological properties. The gating properties of these channels and their modulation by chemical agents, however, are still poorly understood. This review summarizes some aspects of molluscan muscle function with particular reference to the heart ventricle muscle of the pond snail,Lymnaea stagnalis.     

Tachykinins in regulation of gastric motility and secretion

The tachykinins constitute a family of neuropeptides with a common C-terminal amino acid sequence. The best known tachykinin is substance P. Tachykinins are found in the nerve plexuses and nerve fibers in the stomach of all species examined. The circular muscle layer is densely innervated, whereas the longitudinal layer and the mucosa are less intensively innervated. Tachykinins are also found in a significant number of afferent neurons with cell bodies in the dorsal root ganglia. Release of tachykinin can be demonstrated in response to both electrical stimulation of the vagus nerves and application of capsaicin. In the stomach all three known tachykinin receptors seem to be present. Although species variations exist, NK-2 receptors are generally present on the musculature, NK-1 receptors on both neurons and muscles, and NK-3 receptors on neurons only. Tachykinins stimulate motility in all parts of the stomach, but tachykinins also appear to inhibit motility in certain situations. Also, motility initiated centrally, mediated through the vagus nerves, is influenced by tachykinins. The precise role of tachykinin in the various motor programs in the stomach is not clear. Gastric acid secretion is influenced by tachykinins in several species. Tachykinins do not seem to act as neurotransmitters directly on parietal cells, but may have a modulatory function. The importance of tachykinins for the regulation of pepsinogen and hormone secretion from the stomach remains unclear. Received 24 August 1999; received after revision 1 December 1999; accepted 3 December 1999     

Acetyl-coenzyme A synthetase (AMP forming)

Acetyl-coenzyme A synthetase (AMP forming; Acs) is an enzyme whose activity is central to the metabolism of prokaryotic and eukaryotic cells. The physiological role of this enzyme is to activate acetate to acetyl-coenzyme A (Ac-CoA). The importance of Acs has been recognized for decades, since it provides the cell the two-carbon metabolite used in many anabolic and energy generation processes. In the last decade researchers have learned how carefully the cell monitors the synthesis and activity of this enzyme. In eukaryotes and prokaryotes, complex regulatory systems control acs gene expression as a function carbon flux, with a second layer of regulation exerted posttranslationally by the NAD⁺/sirtuin-dependent protein acetylation/deacetylation system. Recent structural work provides snapshots of the dramatic conformational changes Acs undergoes during catalysis. Future work on the regulation of acs gene expression will expand our understanding of metabolic integration, while structure/function studies will reveal more details of the function of this splendid molecular machine.Received 4 December 2003; received after revision 2 March 2004; accepted 16 March 2004     

Calcium-induced calcium release mechanism in vascular smooth muscles — assessments based on contractions evoked in intact and saponin-treated skinned muscles

Summary This article was concerned with the role of Ca in triggering the contraction in vascular smooth muscles. Whenever Ca influx is activated, this Ca does not directly activate the contractile proteins, but rather triggers the release of Ca from the SR to activate calmodulin. This release of Ca by Ca is dependent on the amount of Ca stored within the cells.Voltage dependent Ca influx activated by excess concentrations of K, electrical depolarization and Ca spikes is required to produce the contraction through activation of the Ca-induced Ca release mechanism. The elucidation of the contribution of the P-I response for Ca mobilization through activation of receptors under physiological conditions hopefully will lend support to our hypothesis.     

Calcium-induced calcium release mechanism in vascular smooth muscles--assessments based on contractions evoked in intact and saponin-treated skinned muscles

This article was concerned with the role of Ca in triggering the contraction in vascular smooth muscles. Whenever Ca influx is activated, this Ca does not directly activate the contractile proteins, but rather triggers the release of Ca from the SR to activate calmodulin. This release of Ca by Ca is dependent on the amount of Ca stored within the cells. Voltage dependent Ca influx activated by excess concentrations of K, electrical depolarization and Ca spikes is required to produce the contraction through activation of the Ca-induced Ca release mechanism. The elucidation of the contribution of the P-I response for Ca mobilization through activation of receptors under physiological conditions hopefully will lend support to our hypothesis.     

Fatigue in neuromuscular disorders: focus on Guillain–Barré syndrome and Pompe disease

Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain–Barré syndrome and Pompe disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but in reaction to neuromuscular disease fatigue of central origin can be an important protective mechanism to restrict further damage. In most cases, severity of fatigue seems to be related with disease severity, possibly with the exception of fatigue occurring in a monophasic disorder like Guillain–Barré syndrome. Treatment of fatigue in neuromuscular disease starts with symptomatic treatment of the underlying disease. When symptoms of fatigue persist, non-pharmacological interventions, such as exercise and cognitive behavioral therapy, can be initiated.     

Peptide synthesis through evolution

Ribosome-catalyzed peptide bond formation is a crucial function of all organisms. The ribosome is a ribonucleoprotein particle, with both RNA and protein components necessary for the various steps leading to protein biosynthesis. Evolutionary theory predicts an early environment devoid of complex biomolecules, and prebiotic peptide synthesis would have started in a simple way. A fundamental question regarding peptide synthesis is how the current ribosome-catalyzed reaction evolved from a primitive system. Here we look at both prebiotic and modern mechanisms of peptide bond formation and discuss recent experiments that aim to connect these activities. In particular, RNA can facilitate peptide bond formation by providing a template for activated amino acids to react and can catalyze a variety of functions that would have been necessary in a pre-protein world. Therefore, RNA may have facilitated the emergence of the current protein world from an RNA or even prebiotic world.Received 4 December 2003; received after revision 13 January 2004; accepted 15 January 2004     

A review of the electrophysiological, pharmacological and single channel properties of heart ventricle muscle cells in the snail Lymnaea stagnalis.

Although a considerable body of information has accumulated describing the pharmacological properties of a wide range of molluscan muscle types, the physiological bases underlying these properties have not been thoroughly investigated. At present, little is known about the types of ion channels and their regulation in molluscan muscle cell membranes. Voltage-clamp, and more recently, patch-clamp techniques have revealed molluscan muscles possess a complex array of channel types with various pharmacological and electrophysiological properties. The gating properties of these channels and their modulation by chemical agents, however, are still poorly understood. This review summarizes some aspects of molluscan muscle function with particular reference to the heart ventricle muscle of the pond snail, Lymnaea stagnalis.     

Metabolism and signaling activities of nuclear lipids

Apart from the lipids present in the nuclear envelope, the nucleus also contains lipids which are located further inside and are resistant to treatment with nonionic detergents. Evidence is being accumulated on the importance of internal nuclear lipid metabolism. Nuclear lipid metabolism gives rise to several lipid second messengers that function within the nucleus. Moreover, it is beginning to emerge that nuclear lipids not only act as precursors of bioactive second messengers but may be directly involved in regulation of nuclear structure and gene expression. Over the last 10years, especially the role of the inositol lipid cycle in nuclear signal transduction has been extensively studied. This cycle is activated following a variety of stimuli and is regulated independently from the inositide cycle located at the plasma membrane. However, the nucleus contain other lipids, such as phosphatidylcholine, sphingomyelin, fatty acids and eicosanoids. There are numerous reports which suggest that these classes of nuclear lipids may play roles in the nucleus as important as those of phosphoinositides. This review aims at highlighting the most important aspects regarding the metabolism and signaling activities of nuclear phosphatidylcholine, sphingomyelin, fatty acids and eicosanoids.Received 7 November 2003; received after revision 18 December 2003; accepted 29 December 2003     

The muscle ultrastructure: a structural perspective of the sarcomere

Muscle ultrastructure is characterised by a complex arrangement of many protein-protein interactions. The sarcomere is the basic repeating unit of muscle, formed by two transverse filament systems: the thick and thin filaments. While actin and myosin are the main contractile elements of the sarcomere, other proteins act as scaffolds, control ultrastructure composition, regulate muscle contraction, and transmit tension between sarcomeres and hence to the whole myofibril. Elucidation of the structures of muscle proteins by X-ray crystallography and nuclear magnetic resonance spectroscopy has been essential in understanding muscle contraction, enabling us to relate biological to structural information. These structures reveal how components of the muscle interact, how different factors influence conformational changes within these proteins, and how mutant muscle proteins may interfere with the regulatory fine-tuning of the contractile machinery, hence leading to disease in some cases. Here, structures solved within the sarcomere have been reviewed in order to put the numerous components into context.Received 28 June 2004; received after revision 25 July 2004; accepted 28 July 2004     

The response of human skeletal muscle tissue to hypoxia

Hypoxia refers to environmental or clinical settings that potentially threaten tissue oxygen homeostasis. One unique aspect of skeletal muscle is that, in addition to hypoxia, oxygen balance in this tissue may be further compromised when exercise is superimposed on hypoxia. This review focuses on the cellular and molecular responses of human skeletal muscle to acute and chronic hypoxia, with emphasis on physical exercise and training. Based on published work, it is suggested that hypoxia does not appear to promote angiogenesis or to greatly alter oxidative enzymes in skeletal muscle at rest. Although the HIF-1 pathway in skeletal muscle is still poorly documented, emerging evidence suggests that muscle HIF-1 signaling is only activated to a minor degree by hypoxia. On the other hand, combining hypoxia with exercise appears to improve some aspects of muscle O₂ transport and/or metabolism.     

Magnetic resonance microscopy: in vivo sectioning of a developing insect

Summary The utility of magnetic resonance imaging vis-a-vis insect morphology and development was investigated. MRI is a noninvasive technique that distinguishes between tissues based on proton content and proton environment. At present a resolution of 100 m is achievable. The technique avoids fixation artifacts and allows the detection of motion within the organism.