Publications
39 results found
Barclay CJ, Curtin NA, 2022, The legacy of A. V. Hill's Nobel Prize winning work on muscle energetics., J Physiol, Vol: 600, Pages: 1555-1578
A. V. Hill was awarded the 1922 Nobel Prize, jointly with Otto Meyerhof, for Physiology or Medicine for his work on energetic aspects of muscle contraction. Hill used his considerable mathematical and experimental skills to investigate the relationships among muscle mechanics, biochemistry and heat production. The main ideas of the work for which the Nobel Prize was awarded were superseded within a decade, and the legacy of Hill and Meyerhof's Nobel work was not a set of persistent, influential ideas but rather a prolonged period of extraordinary activity that advanced the understanding of how muscles work far beyond the concepts that led to the Nobel Prize. Hill pioneered the integration of mathematics into the study of physiology and pharmacology. Particular aspects of Hill's own work that remain in common use in muscle physiology include mathematical descriptions of the relationships between muscle force output and shortening velocity and between force output and calcium concentration, and the model of muscle as a contractile element in series with an elastic element. We describe some of the characteristics of Hill's broader scientific activities and then outline how Hill's work on muscle energetics was extended after 1922, as a result of Hill's own work and that of others, to the present day.
Curtin NA, Woledge RC, West TG, et al., 2019, Energy turnover in mammalian skeletal muscle in contractions mimicking locomotion: effects of stimulus pattern on work, impulse and energetic cost and efficiency, The Journal of Experimental Biology, Vol: 222, ISSN: 0022-0949
Active muscle performs various mechanical functions during locomotion: work output during shortening, work absorption when resisting (but not preventing) lengthening, and impulse (force-time integral) whenever there is active force. The energetic costs of these functions are important components in the energy budget during locomotion.We investigated how the pattern of stimulation and movement affected the mechanics and energetics of muscle fibre bundles isolated from wild rabbits (Oryctolagus cuniculus, Linnaeus). The fibres were from muscles consisting of mainly fast-twitch, type-2 fibres. Fibre length was either held constant (isometric) or a sinusoidal pattern of movement was imposed at a frequency similar to the stride frequency of running wild rabbits. Duty cycle (=stimulation duration x movement frequency) and phase (timing of stimulation relative to movement) were varied. Work and impulse were measured as well as energy produced as heat. The sum of net work (work output - work input) and heat was taken as a measure of energetic cost.Maximum work output was produced with a long duty cycle and stimulation starting slightly before shortening and was produced quite efficiently. However, efficiency was even higher with other stimulation patterns that produced less work. The highest impulse (considerably higher than isometric impulse) was produced when stimulation started while the muscle fibres were being lengthened. High impulse was produced very economically due to the low cost of producing force during lengthening.Thus, locomotion demanding high work, high impulse or economical work output or impulse, each require a distinct and different pattern of stimulation and movement.
Curtin NA, Bartlam-Brooks HLA, Hubel TY, et al., 2018, Remarkable muscles, remarkable locomotion in desert-dwelling wildebeest, Nature, Vol: 563, Pages: 393-396, ISSN: 0028-0836
Large mammals that live in arid and/or desert environments can cope with seasonal and local variations in rainfall, food and climate1 by moving long distances, often without reliable water or food en route. The capacity of an animal for this long-distance travel is substantially dependent on the rate of energy utilization and thus heat production during locomotion-the cost of transport2-4. The terrestrial cost of transport is much higher than for flying (7.5 times) and swimming (20 times)4. Terrestrial migrants are usually large1-3 with anatomical specializations for economical locomotion5-9, because the cost of transport reduces with increasing size and limb length5-7. Here we used GPS-tracking collars10 with movement and environmental sensors to show that blue wildebeest (Connochaetes taurinus, 220 kg) that live in a hot arid environment in Northern Botswana walked up to 80 km over five days without drinking. They predominantly travelled during the day and locomotion appeared to be unaffected by temperature and humidity, although some behavioural thermoregulation was apparent. We measured power and efficiency of work production (mechanical work and heat production) during cyclic contractions of intact muscle biopsies from the forelimb flexor carpi ulnaris of wildebeest and domestic cows (Bos taurus, 760 kg), a comparable but relatively sedentary ruminant. The energetic costs of isometric contraction (activation and force generation) in wildebeest and cows were similar to published values for smaller mammals. Wildebeest muscle was substantially more efficient (62.6%) than the same muscle from much larger cows (41.8%) and comparable measurements that were obtained from smaller mammals (mouse (34%)11 and rabbit (27%)). We used the direct energetic measurements on intact muscle fibres to model the contribution of high working efficiency of wildebeest muscle to minimizing thermoregulatory challenges during their long migrations under hot arid c
Wilson AM, Hubel TY, Wilshin SD, et al., 2018, Biomechanics of predator-prey arms race in lion, zebra, cheetah and impala., Nature, Vol: 554, Pages: 183-188
The fastest and most manoeuvrable terrestrial animals are found in savannah habitats, where predators chase and capture running prey. Hunt outcome and success rate are critical to survival, so both predator and prey should evolve to be faster and/or more manoeuvrable. Here we compare locomotor characteristics in two pursuit predator-prey pairs, lion-zebra and cheetah-impala, in their natural savannah habitat in Botswana. We show that although cheetahs and impalas were universally more athletic than lions and zebras in terms of speed, acceleration and turning, within each predator-prey pair, the predators had 20% higher muscle fibre power than prey, 37% greater acceleration and 72% greater deceleration capacity than their prey. We simulated hunt dynamics with these data and showed that hunts at lower speeds enable prey to use their maximum manoeuvring capacity and favour prey survival, and that the predator needs to be more athletic than its prey to sustain a viable success rate.
Curtin NA, Diack RA, West TG, et al., 2015, Skinned fibres produce the same power and force as intact fibre bundles from muscle of wild rabbits., Journal of Experimental Biology, Vol: 218, Pages: 2856-2863, ISSN: 1477-9145
Skinned fibres have advantages for comparing the muscle properties of different animal species because they can be prepared from a needle biopsy taken under field conditions. However, it is not clear how well the contractile properties of skinned fibres reflect the properties of the muscle fibres in vivo. Here, we compare the mechanical performance of intact fibre bundles and skinned fibres from muscle of the same animals. This is the first such direct comparison. Maximum power and isometric force were measured at 25°C using peroneus longus (PL) and extensor digiti-V (ED-V) muscles from wild rabbits (Oryctolagus cuniculus). More than 90% of the fibres in these muscles are fast-twitch, type 2 fibres. Maximum power was measured in force-clamp experiments. We show that maximum power per volume was the same in intact (121.3±16.1 W l(-1), mean±s.e.m.; N=16) and skinned (122.6±4.6 W l(-1); N=141) fibres. Maximum relative power (power/FIM Lo, where FIM is maximum isometric force and Lo is standard fibre length) was also similar in intact (0.645±0.037; N=16) and skinned (0.589±0.019; N=141) fibres. Relative power is independent of volume and thus not subject to errors in measurement of volume. Finally, maximum isometric force per cross-sectional area was also found to be the same for intact and skinned fibres (181.9 kPa±19.1; N=16; 207.8 kPa±4.8; N=141, respectively). These results contrast with previous measurements of performance at lower temperatures where skinned fibres produce much less power than intact fibres from both mammals and non-mammalian species.
Zolfaghari PS, Carré JE, Parker N, et al., 2015, Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis., Am J Physiol Endocrinol Metab, Vol: 308, Pages: E713-E725
Muscle dysfunction is a common feature of severe sepsis and multiorgan failure. Recent evidence implicates bioenergetic dysfunction and oxidative damage as important underlying pathophysiological mechanisms. Increased abundance of uncoupling protein-3 (UCP3) in sepsis suggests increased mitochondrial proton leak, which may reduce mitochondrial coupling efficiency but limit reactive oxygen species (ROS) production. Using a murine model, we examined metabolic, cardiovascular, and skeletal muscle contractile changes following induction of peritoneal sepsis in wild-type and Ucp3(-/-) mice. Mitochondrial membrane potential (Δψm) was measured using two-photon microscopy in living diaphragm, and contractile function was measured in diaphragm muscle strips. The kinetic relationship between membrane potential and oxygen consumption was determined using a modular kinetic approach in isolated mitochondria. Sepsis was associated with significant whole body metabolic suppression, hypothermia, and cardiovascular dysfunction. Maximal force generation was reduced and fatigue accelerated in ex vivo diaphragm muscle strips from septic mice. Δψm was lower in the isolated diaphragm from septic mice despite normal substrate oxidation kinetics and proton leak in skeletal muscle mitochondria. Even though wild-type mice exhibited an absolute 26 ± 6% higher UCP3 protein abundance at 24 h, no differences were seen in whole animal or diaphragm physiology, nor in survival rates, between wild-type and Ucp3(-/-) mice. In conclusion, this murine sepsis model shows a hypometabolic phenotype with evidence of significant cardiovascular and muscle dysfunction. This was associated with lower Δψm and alterations in mitochondrial ATP turnover and the phosphorylation pathway. However, UCP3 does not play an important functional role, despite its upregulation.
West TG, Toepfer CN, Woledge RC, et al., 2013, Power output of skinned skeletal muscle fibres from the cheetah (Acinonyx jubatus), JOURNAL OF EXPERIMENTAL BIOLOGY, Vol: 216, Pages: 2974-2982, ISSN: 0022-0949
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- Citations: 15
Song W, Vikhorev PG, Kashyap MN, et al., 2013, Mechanical and energetic properties of papillary muscle from ACTC E99K transgenic mouse models of hypertrophic cardiomyopathy, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 304, Pages: H1513-H1524, ISSN: 0363-6135
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- Citations: 20
Mansfield C, West TG, Curtin NA, et al., 2012, Stretch of Contracting Cardiac Muscle Abruptly Decreases the Rate of Phosphate Release at High and Low Calcium, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 287, Pages: 25696-25705, ISSN: 0021-9258
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- Citations: 13
Park-Holohan S, Linari M, Reconditi M, et al., 2012, Mechanics of myosin function in white muscle fibres of the dogfish, Scyliorhinus canicula, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 590, Pages: 1973-1988, ISSN: 0022-3751
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- Citations: 12
Bickham DC, West TG, Webb MR, et al., 2011, Millisecond-scale biochemical response to change in strain., Biophysical Journal
Barclay CJ, Woledge RC, Curtin NA, 2010, Is the efficiency of mammalian (mouse) skeletal muscle temperature dependent?, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 588, Pages: 3819-3831, ISSN: 0022-3751
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- Citations: 46
Park-Holohan S-J, West TG, Woledge RC, et al., 2010, Effect of phosphate and temperature on force exerted by white muscle fibres from dogfish, JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY, Vol: 31, Pages: 35-44, ISSN: 0142-4319
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- Citations: 5
Curtin NA, Lou F, Woledge RC, 2010, Sustained performance by red and white muscle fibres from the dogfish Scyliorhinus canicula, JOURNAL OF EXPERIMENTAL BIOLOGY, Vol: 213, Pages: 1921-1929, ISSN: 0022-0949
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- Citations: 5
Loiselle DS, Tran K, Crampin EJ, et al., 2010, Why has reversal of the actin-myosin cross-bridge cycle not been observed experimentally?, J Appl Physiol (1985), Vol: 108, Pages: 1465-1471
We trace the history of attempts to determine whether the experimentally observed diminution of metabolic energy expenditure when muscles lengthen during active contraction is consistent with reversibility of biochemical reactions and, in particular, with the regeneration of ATP. We note that this scientific endeavor has something of a parallel flavor to it, with both early and more recent experiments exploiting both isolated muscle preparations and exercising human subjects. In tracing this history from the late 19th century to the present, it becomes clear that energy can be (at least transiently) stored in a muscle undergoing an eccentric contraction but that this is unlikely to be due to the regeneration of ATP. A recently developed, thermodynamically constrained model of the cross-bridge cycle provides additional insight into this conclusion.
Barclay CJ, Woledge RC, Curtin NA, 2010, Inferring crossbridge properties from skeletal muscle energetics, PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, Vol: 102, Pages: 53-71, ISSN: 0079-6107
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- Citations: 62
Woledge RC, Barclay CJ, Curtin NA, 2009, Temperature change as a probe of muscle crossbridge kinetics: a review and discussion, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 276, Pages: 2685-2695, ISSN: 0962-8452
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- Citations: 31
Barclay CJ, Woledge RC, Curtin NA, 2009, Effects of UCP3 genotype, temperature and muscle type on energy turnover of resting mouse skeletal muscle., Pflugers Arch, Vol: 457, Pages: 857-864, ISSN: 0031-6768
Uncoupling protein 3 (UCP3) is a mitochondrial transporter protein which, when over-expressed in mice, is associated with increased metabolic rate, increased feeding and low body weight. This phenotype probably reflects the increased levels of UCP3 partially uncoupling mitochondrial respiration from cellular ATP demands. Consistent with that, mitochondria isolated from muscles of mice that over-express UCP3 are less tightly coupled than those from wild-type mice but the degree of uncoupling is not modulated by likely physiological regulatory factors. To determine whether this also applies to intact muscle fibres, we tested the hypothesis that UCP3 constitutively (i.e. in an unregulated fashion) uncouples mitochondria in muscles from mice that over-expressed human UCP3 (OE mice). The rate of heat production of resting muscles was measured in vitro using bundles of fibres from soleus and extensor digitorum longus muscles of OE, wild-type (WT) and UCP3 knock-out mice. At 20 degrees C, the only significant effect of genotype was that the rate of heat production of OE soleus (3.04+/-0.16 mW g(-1)) was greater than for WT soleus (2.31+/-0.05 mW g(-1)). At physiological temperature (35 degrees C), the rate of heat production was independent of genotype and equal to the expected in vivo rate for skeletal muscles of WT mice. We conclude that at 35 degrees C, the transgenic UCP3 was not constitutively active, but at 20 degrees C in slow-twitch muscle, it was partially activated by unknown factors. The physiological factor(s) that activate mitochondrial uncoupling by UCP3 in vivo was either not present or inactive in resting isolated muscles.
Foster K, Graham IR, Otto A, et al., 2009, Adeno-associated virus-8-mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow byt not fast muscle, Rejuvenation Research, Vol: 12, Pages: 85-93
Barclay CJ, Lichtwark GA, Curtin NA, 2008, The energetic cost of activation in mouse fast-twitch muscle is the same whether measured using reduced filament overlap or N-benzyl-p-toluenesulphonamide., Acta Physiol (Oxf), Vol: 193, Pages: 381-391
AIM: Force generation and transmembrane ion pumping account for the majority of energy expended by contracting skeletal muscles. Energy turnover for ion pumping, activation energy turnover (E(A)), can be determined by measuring the energy turnover when force generation has been inhibited. Most measurements show that activation accounts for 25-40% of isometric energy turnover. It was recently reported that when force generation in mouse fast-twitch muscle was inhibited using N-benzyl-p-toluenesulphonamide (BTS), activation accounted for as much as 80% of total energy turnover during submaximal contractions. The purpose of this study was to compare E(A) measured by inhibiting force generation by: (1) the conventional method of reducing contractile filament overlap; and (2) pharmacological inhibition using BTS. METHODS: Experiments were performed in vitro using bundles of fibres from mouse fast-twitch extensor digitorum longus (EDL) muscle. Energy turnover was quantified by measuring the heat produced during 1-s maximal and submaximal tetanic contractions at 20 and 30 degrees C. RESULTS: E(A) measured using reduced filament overlap was 0.36 +/- 0.04 (n = 8) at 20 degrees C and 0.31 +/- 0.05 (n = 6) at 30 degrees C. The corresponding values measured using BTS in maximal contractions were 0.46 +/- 0.06 and 0.38 +/- 0.06 (n = 6 in both cases). There were no significant differences among these values. E(A) was also no different when measured using BTS in submaximal contractions. CONCLUSION: Activation energy turnover is the same whether measured using BTS or reduced filament overlap and accounts for slightly more than one-third of isometric energy turnover in mouse EDL muscle.
Barclay CJ, Woledge RC, Curtin NA, 2007, Energy turnover for Ca+2 cycling in skeletal muscle, JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY, Vol: 28, Pages: 259-274, ISSN: 0142-4319
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- Citations: 85
West TG, Ferenczi MA, Woledge RC, et al., 2005, Influence of ionic strength on the time course of force development and phosphate release by dogfish muscle fibres, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 567, Pages: 989-1000, ISSN: 0022-3751
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- Citations: 14
Curtin NA, Woledge RC, Aerts P, 2005, Muscle directly meets the vast power demands in agile lizards., Proc Biol Sci, Vol: 272, Pages: 581-584, ISSN: 0962-8452
Level locomotion in small, agile lizards is characterized by intermittent bursts of fast running. These require very large accelerations, often reaching several times g. The power input required to increase kinetic energy is calculated to be as high as 214 W kg(-1) muscle (+/-20 W kg(-1) s.e.; averaged over the complete locomotor cycle) and 952 W kg(-1) muscle (+/-89 W kg(-1) s.e.; instantaneous peak power). In vitro muscle experiments prove that these exceptional power requirements can be met directly by the lizard's muscle fibres alone; there is no need for mechanical power amplifying mechanisms.
Curtin NA, Lou F, Woledge RC, 2005, Predicting red muscle performance, Symposium on Locomotory Muscle Function and Control held at the 10th Benelux Congress for Zoology, Pages: 59-70
The active force production during contraction of bundles of red muscle fibres from myotomal muscle of dogfish Scyliorhinus canicula (L.) has been predicted by a numerical model based on Hill's 2-component model of the mechanical properties of muscle, with the addition of a simple model for the kinetics of activation. When all of these factors are included, the model makes good predictions for the force and power during stimulation. There are, however, significant discrepancies during relaxation after the end of stimulation, from which we conclude that additional processes have a large influence on force during relaxation. This has functional relevance for fish swimming because during relaxation the muscle fibre Continues its sinusoidal pattern of movement and thus continues to either produce power if shortening, or require power input from other structures to cause lengthening.
West TG, Curtin NA, Ferenczi MA, et al., 2004, Actomyosin energy turnover declines while force remains constant during isometric muscle contraction, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 555, Pages: 27-43, ISSN: 0022-3751
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- Citations: 28
Linari M, Woledge RC, Curtin NA, 2003, Energy storage during stretch of active single fibres from frog skeletal muscle., J Physiol, Vol: 548, Pages: 461-474, ISSN: 0022-3751
Heat production and force were measured during tetani of single muscle fibres from anterior tibialis of frog. During stimulation fibres were either kept under isometric conditions, or were stretched or allowed to shorten (at constant velocity) after isometric force had reached its plateau value. The energy change was evaluated as the sum of heat and work (work = integral of force with respect to length change). Net energy absorption occurred during stretch at velocities greater than about 0.35 L0 s-1 (L0 is fibre length at resting sarcomere length 2.10 microm). Heat produced by 1 mm segments of the fibre was measured simultaneously and separately; energy absorption is not an artefact due to patchy heat production. The maximum energy absorption, 0.092 +/- 0.002 P0L0 (mean +/- S.E.M., n = 8; where P0 is isometric force at L0), occurred during the fastest stretches (1.64 L0 s-1) and amounted to more than half of the work done on the fibre. Energy absorption occurred in two phases. The amount in the first phase, 0.027 +/- 0.003 P0L0 (n = 32), was independent of velocity beyond 0.18 L0 s-1. The quantity absorbed in the second phase increased with velocity and did not reach a limiting value in the range of velocities used. After stretch, energy was produced in excess of the isometric rate, probably from dissipation of the stored energy. About 34 % (0.031 P0L0/0.092 P0L0) of the maximum absorbed energy could be stored elastically (in crossbridges, tendons, thick, thin and titin filaments) and by redistribution of crossbridge states. The remaining energy could have been stored in stretching transverse, elastic connections between myofibrils.
Curtin NA, West TG, Ferenczi MA, et al., 2003, Rate of actomyosin ATP hydrolysis diminishes during isometric contraction, MOLECULAR AND CELLULAR ASPECTS OF MUSCLE CONTRACTION, Vol: 538, Pages: 613-626, ISSN: 0065-2598
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- Citations: 3
Woledge RC, Curtin NA, Rall JA, 2003, Molecular and cellular aspects of muscle contraction. General discussion part III., Adv Exp Med Biol, Vol: 538, Pages: 671-688, ISSN: 0065-2598
Woledge RC, Curtin NA, Linari M, 2003, Energy storage during stretch of active single fibres., Adv Exp Med Biol, Vol: 538, Pages: 627-633, ISSN: 0065-2598
Curtin NA, West TG, Ferenczi MA, et al., 2003, Rate of actomyosin ATP hydrolysis diminishes during isometric contraction., Molecular and Cellular Aspects of Muscle Contraction, Editors: Sugi, Publisher: Kluwer Academic Plenum Publishers, New York, Pages: 613-625, ISBN: 9780306478703
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