Arthur Cheng

Arthur Cheng
York University · School of Kinesiology and Health Sciences

PhD

About

90
Publications
16,801
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,487
Citations
Citations since 2016
41 Research Items
1241 Citations
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
Introduction
My primary research interest is investigating the cellular mechanisms of skeletal muscle fatigue and recovery. I also have a great interest in investigating the mechanisms of muscle weakness in chronic diseases, the cellular adaptations to high-intensity and endurance training, and how nutritional interventions affect intracellular calcium handling and muscle contractile force.

Publications

Publications (90)
Article
Full-text available
The contractile function of skeletal muscle declines during intense or prolonged physical exercise, that is, fatigue develops. Skeletal muscle fibers fatigue acutely during highly intense exercise when they have to rely on anaerobic metabolism. Early stages of fatigue involve impaired myofibrillar function, whereas decreased Ca(2+) release from the...
Article
Mechanical dissection of single intact mammalian skeletal muscle fibers permits real-time measurement of intracellular properties and contractile function of living fibers. A major advantage of mechanical over enzymatic fiber dissociation is that single fibers can be isolated with their tendons remaining attached, which allows contractile forces (i...
Article
Full-text available
Key points: We investigated whether intramuscular temperature affects the acute recovery of exercise performance following fatigue-induced by endurance exercise. Mean power output was better preserved during an all-out arm-cycling exercise following a 2 h recovery period in which the upper arms were warmed to an intramuscular temperature of ̴ 38°C...
Article
Full-text available
Key points: We have systematically investigated how defects in muscle contractile function contribute to weakness in ALS. Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force. On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracel...
Article
Full-text available
Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on muscle weakness associated with RA. Oxidative stress has been implicated in the disease pathogenesis of RA. Here we show that oxidative post-translation...
Article
Full-text available
Exercise is one of the only non-pharmacologic remedies known to counteract genetic and chronic diseases by enhancing health and improving life span. Although the many benefits of regular physical activity have been recognized for some time, the intricate and complex signalling system triggered at the onset of exercise have only recently begun to be...
Article
Cells rapidly lose their physiological phenotype upon disruption of their extracellular matrix (ECM)-intracellular cytoskeleton interactions. By comparing adult mouse skeletal muscle fibers isolated either by mechanical dissection or by collagenase-induced ECM digestion, we investigated acute effects of ECM disruption on cellular and mitochondrial...
Article
Full-text available
Background: Activation of sphingomyelinase (SMase) as a result of a general inflammatory response has been implicated as a mechanism underlying disease-related loss of skeletal muscle mass and function in several clinical conditions including heart failure. Here, for the first time, we characterize the effects of SMase activity on human muscle fib...
Article
Full-text available
The application of post-exercise cooling (e.g., cold water immersion) and post-exercise heating has become a popular intervention which is assumed to increase functional recovery and may improve chronic training adaptations. However, the effectiveness of such post-exercise temperature manipulations remains uncertain. The aim of this comprehensive r...
Article
Full-text available
Background: Patients with breast cancer exhibit muscle weakness, which is associated with increased mortality risk and reduced quality of life. Muscle weakness is experienced even in the absence of loss of muscle mass in breast cancer patients, indicating intrinsic muscle dysfunction. Physical activity is correlated with reduced cancer mortality a...
Article
Full-text available
The hypoxia‐inducible nuclear‐encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4‐like 2 (NDUFA4L2) has been demonstrated to decrease oxidative phosphorylation and production of reactive oxygen species in neonatal cardiomyocytes, brain tissue and hypoxic domains of cancer cells. Prolonged local hypoxia can negatively...
Article
Accumulating evidence now shows that supplemental antioxidants including vitamin C, vitamin E and N-Acetylcysteine consumption can suppress adaptations to endurance-type exercise by attenuating reactive oxygen and nitrogen species (RONS) formation within skeletal muscle. This emerging evidence points to the importance of pro-oxidation as an importa...
Article
Full-text available
Purpose Carbohydrate (CHO) restriction could be a potent metabolic regulator of endurance exercise-induced muscle adaptations. Here, we determined whether post-exercise CHO restriction following strenuous exercise combining continuous cycling exercise (CCE) and sprint interval exercise could affect the gene expression related to mitochondrial bioge...
Preprint
Full-text available
Cells rapidly lose their physiological phenotype upon isolation from their native microenvironment. Here, we investigated the role of the extracellular matrix (ECM) for mitochondrial morphology and Ca2+ handling in adult mouse skeletal muscle fibres. Adult skeletal muscle fibres were isolated from mouse toe muscle either by collagenase-induced diss...
Article
Full-text available
Activity dependent potentiation is thought to result from phosphorylation of the regulatory light chains of myosin, increasing Ca2+ sensitivity. Yet, Ca2+ sensitivity decreases early in a period of intermittent contractions. The purpose of this study was to investigate the early change in Ca2+ sensitivity during intermittent submaximal tetanic cont...
Article
Full-text available
Background: Muscle weakness is a common symptom in numerous diseases and a regularly occurring problem associated with ageing. Prolonged low-frequency force depression (PLFFD) is a form of exercise-induced skeletal muscle weakness observed after exercise. Three different intramuscular mechanisms underlying PLFFD have been identified: decreased sar...
Article
Full-text available
Prolonged low‐frequency force depression (PLFFD) induced by fatiguing exercise is characterized by a persistent depression in submaximal contractile force during the recovery period. Muscle glycogen depletion is known to limit physical performance during prolonged low‐ and moderate‐intensity exercise, and accelerating glycogen re‐synthesis with pos...
Article
Full-text available
Strenuous exercise is a potent stimulus to induce beneficial skeletal muscle adaptations, ranging from increased endurance due to mitochondrial biogenesis and angiogenesis, to increased strength from hypertrophy. While exercise is necessary to trigger and stimulate muscle adaptations, the post-exercise recovery period is equally critical in providi...
Chapter
Measuring free Ca²⁺ concentration ([Ca²⁺]) in the cytosol or organelles is routine in many fields of research. The availability of membrane permeant forms of indicators coupled with the relative ease of transfecting cell lines with biological Ca²⁺ sensors have led to the situation where cellular and subcellular [Ca²⁺] is examined by many non-specia...
Article
Key points: Changes in intramuscular Ca2+ handling contribute to development of fatigue and disease-related loss of muscle mass and function. To date, no data on human intact living muscle fibres have been described. We manually dissected intact single fibres from human intercostal muscle and simultaneously measured force and myoplasmic free [Ca2+...
Article
Full-text available
Background: Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is predicted that controlling muscle atrophy can reduce morbidity and mortality associated with diseases such as cancer cachexia and sarcopenia. Methods: We analyzed gene exp...
Article
Purpose: The extracellular K+ concentration ([K+]o) increases during physical exercise. We here studied whether moderately elevated [K+]o may increase force and power output during contractions at in vivo-like sub-tetanic frequencies and whether such potentiation was associated with increased free cytosolic [Ca2+] ([Ca2+]i) during contractions. M...
Article
Full-text available
Key points: Skeletal muscle fatigue limits performance in various physical activities, with exercise intolerance being a key symptom in a broad spectrum of diseases. We investigated whether a small molecule fast skeletal troponin activator (FSTA), CK-2066260, can mitigate muscle fatigue by reducing the cytosolic free [Ca2+ ] required to produce a...
Article
Full-text available
Effective practices to improve skeletal muscle fatigue resistance are crucial for athletes as well as patients with dysfunctional muscles. To this end, it is important to identify the cellular signaling pathway that triggers mitochondrial biogenesis and thereby increases oxidative capacity and fatigue resistance in skeletal muscle fibers. Here, we...
Article
Discrepant results have been reported regarding an intramuscular mechanism underlying the ergogenic effect of caffeine on neuromuscular function in humans. Here, we reevaluated the effect of caffeine on muscular force production in humans and combined this with measurements of the caffeine dose-response relationship on force and cytosolic free [Ca2...
Article
Skeletal muscle weakness is a comorbidity in patients with rheumatoid arthritis (RA), which impairs the ability to work and leads to reduced quality of life for the afflicted patients. However, little molecular insight is available on RA-induced muscle weakness. The reactive oxygen/nitrogen species peroxynitrite (ONOO-) can induce oxidative post-tr...
Article
Full-text available
Rheumatoid arthritis (RA) is a chronic, inflammatory disease that affects 1% of the general population. Fatigue is a common complaint of patients with RA, however their perceived fatigue may be more exacerbated than objective measures of fatigue may indicate. The assessment of fatigue is made complex due to inconsistent and vague terms used to defi...
Article
Full-text available
Fatigue of single mouse fibers during repeated high-frequency stimulation results initially from decreased Ca2+ sensitivity while free myoplasmic calcium concentration ([Ca2+]m) increases, followed by decreasing [Ca2+]m. Recovery of active force with low-frequency stimulation is slow and persistent fatigue results from low [Ca2+]m. However, the con...
Article
Full-text available
Electrically-evoked low-frequency (submaximal) force is increased immediately following high-frequency stimulation in human skeletal muscle. Although central mechanisms have been suggested to be the major cause of this low-frequency force potentiation, intramuscular factors might contribute. Thus, we hypothesized that two intramuscular Ca2+-depende...
Article
Full-text available
Background Critical illness myopathy is an acquired skeletal muscle disorder with severe myosin loss and muscle weakness frequently seen in intensive care unit (ICU) patients. It is unknown if impaired excitation-contraction coupling contributes to the muscle weakness. Methods We used a unique ICU model where rats were deeply sedated, post-synaptic...
Article
Full-text available
Key points We report that the small molecule CK‐2066260 selectively slows the off‐rate of Ca²⁺ from fast skeletal muscle troponin, leading to increased myofibrillar Ca²⁺ sensitivity in fast skeletal muscle. Rodents dosed with CK‐2066260 show increased hindlimb muscle force and power in response to submaximal rates of nerve stimulation in situ. CK‐2...
Article
Full-text available
The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle...
Article
The production of reactive oxygen/nitrogen species (ROS/RNS) is generally considered to increase during physical exercise. Nevertheless, direct measurements of ROS/RNS often show modest increases in ROS/RNS in muscle fibres even during intensive fatiguing stimulation, and the major source(s) of ROS/RNS during exercise is still being debated. In res...
Article
Full-text available
High-intensity interval training (HIIT) is a time-efficient way of improving physical performance in healthy subjects and in patients with common chronic diseases, but less so in elite endurance athletes. The mechanisms underlying the effectiveness of HIIT are uncertain. Here, recreationally active human subjects performed highly demanding HIIT con...
Article
Full-text available
Muscle weakness and exercise intolerance are hallmark symptoms in mitochondrial disorders. Little is known about the mechanisms leading to impaired skeletal muscle function and ultimately muscle weakness in these patients. In a mouse model of lethal mitochondrial myopathy, the muscle-specific Tfam knock-out (KO) mouse, we previously demonstrated an...
Article
Full-text available
In skeletal muscle, intracellular Ca(2+) is an important regulator of contraction as well as gene expression and metabolic processes. Because of the difficulties to obtain intact human muscle fibers, human myotubes have been extensively employed for studies of Ca(2+)-dependent processes in human adult muscle. Despite this, it is unknown whether the...
Article
Decreased muscle strength is a common consequence of ageing in humans. A decline in muscle force production can affect independent living and the quality of life of aged individuals, especially if muscle weakness impedes with the ability to perform the basic tasks of daily living. The reduction in muscle strength in old age is caused in part by dec...
Article
Full-text available
The findings by Mázala and colleagues help advance the notion that disrupted intracellular Ca(2+) homeostasis is an important trigger for inducing necrosis and pseudo-hypertrophy in muscle dystrophy. Copyright © 2015, American Journal of Physiology - Cell Physiology.
Article
The contractile performance of skeletal muscle declines during intense activities, i.e. fatigue develops. Fatigued muscle can enter a state of prolonged low-frequency force depression (PLFFD). PLFFD can be due to decreased tetanic free cytosolic [Ca2+] ([Ca2+]i) and/or decreased myofibrillar Ca2+ sensitivity. Increases in reactive oxygen and nitrog...
Article
Full-text available
Objective: Skeletal muscle weakness is a prominent clinical feature in patients with rheumatoid arthritis (RA), but the underlying mechanism(s) is unknown. Here we investigate the mechanisms behind arthritis-induced skeletal muscle weakness with special focus on the role of nitrosative stress on intracellular Ca(2+) handling and specific force pro...
Article
In skeletal muscle fibres glycogen has been shown to be stored at different subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii) within the myofibrils (intramyofibrillar); (iii) subsarcolemmal. Of these, intramyofibrillar glycogen has been implied as a critical regulator of sarcoplasmic reticulum Ca2+ release. The aim of the...
Article
The interpolated twitch technique is a practical method used to determine whether impairments in voluntary drive are a limiting factor in the reduction of muscle contractile force during and following fatiguing efforts. This method has been validated and is extensively employed in neuromuscular research, although its accuracy has been questioned (T...
Article
Double discharges (doublets) of motor neurones at the onset of contractions increase both force and rate of force development during voluntary submaximal contractions. The purpose of this study was to examine the role of doublet discharges on force and myoplasmic free [Ca(2+)] ([Ca(2+)]i) during repeated fatiguing contractions, using a stimulation...
Article
Nemaline myopathy is the most common congenital myopathy and is caused by mutations in various genes such as ACTA1 (encoding skeletal α-actin). It is associated with limb and respiratory muscle weakness. Despite increasing clinical and scientific interest, the molecular and cellular events leading to such weakness remain unknown, which prevents the...
Article
Full-text available
Reductions in active joint range of motion (ROM) are responsible for decreased work-generating capacity during fatiguing repetitive isotonic shortening contractions. Factors responsible for impairing the joint-angle-specific net torque developed during muscle shortening could include fatigue-induced torque loss, shortening-induced torque depression...
Article
Mitochondrial dysfunction can drastically impair muscle function with weakness and exercise intolerance as key symptoms. Here, we examine the time course of development of muscle dysfunction in a mouse model of premature ageing induced by defective proofreading function of mitochondrial DNA (mtDNA) polymerase (mtDNA mutator mouse). Isolated fast-tw...
Article
Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca(2+) handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age m...
Article
Full-text available
Antioxidants are assumed to provide numerous benefits, including better health, a reduced rate of aging, and improved exercise performance. Specifically, antioxidants are commonly "prescribed" by the media, supplement industry, and "fitness experts" for individuals prior to training and performance, with assumed benefits of improved fatigue resista...
Conference Paper
Background and objective Muscle weakness is a common symptom in patients with rheumatoid arthritis. In mice with collagen-induced arthritis, (CIA, a mouse model of rheumatoid arthritis) the authors demonstrated that muscle weakness is overwhelmingly due to nitric oxide (NO)-derived radicals modifying myofibrillar proteins (nitrosative stress) in sk...
Article
Measurements of free cytosolic Ca(2+) concentration ([Ca(2+)](i)) or free Ca(2+) concentration in cellular organelles have become more routine. The primary reason for this is the availability of membrane permeant forms of Ca(2+) indicators that can easily enter cells. In this chapter, the properties required of an ideal Ca(2+) indicator are identif...
Article
Previous studies from our laboratory have shown that weakness, rather than decreased endurance, is the main contractile defect in a mouse mitochondrial myopathy model (skeletal muscle-specific Tfam KO mice). Here we used a mouse model with mitochondrial defects induced by knock-in of a proof-reading-deficient version of PolgA. These mice display an...
Article
Full-text available
The effects of postactivation potentiation (PAP) on evoked contractions are well understood, but less is known about the effect of PAP on voluntary submaximal contractions. Using a measure of neuromuscular efficiency (NME) [NME = (mV EMG / Nm torque)] we explored the effects of PAP in the triceps brachii at two muscle lengths. Evoked twitch and NME...
Article
Full-text available
The fatigue-related reduction in joint range of motion (ROM) during dynamic contraction tasks may be related to muscle length-dependent alterations in torque and contractile kinetics, but this has not been systematically explored previously. Twelve young men performed a repetitive voluntary muscle shortening contraction task of the dorsiflexors at...
Article
In addition to torque (force) loss during dynamic fatiguing contractions, an important aspect of fatigue is the reduction in shortening velocity. Relatively few reports have studied changes in shortening velocity in response to fatigue, and inconsistencies in the results might depend on the muscle tested. To better understand fatigue-related change...
Article
The aim was of this study was to determine whether voluntary activation calculated using the interpolated twitch technique (ITT) would be underestimated by muscle length-induced changes in the twitch amplitude evoked at rest after maximum voluntary contraction (MVC) in the elbow extensors. In 12 healthy men, calculated voluntary activations were co...