Does intracellular metabolite diffusion limit post-contractile recovery in burst locomotor muscle?
TL;DR: It is concluded that fiber SA:V and O2 flux exert more control than intracellular metabolite diffusive flux over the developmental changes in metabolic organization and metabolic fluxes that characterize these muscles.
Abstract: Post-metamorphic growth in the blue crab entails an increase in body mass that spans several orders of magnitude. The muscles that power burst swimming in these animals grow hypertrophically, such that small crabs have fiber diameters that are typical of most cells ( 600·µm). Thus, as the animals grow, their muscle fibers cross and greatly exceed the surface area to volume ratio (SA:V) and intracellular diffusion distance threshold that is adhered to by most cells. Large fiber size should not impact burst contractile function, but post-contractile recovery may be limited by low SA:V and excessive intracellular diffusion distances. A number of changes occur in muscle structure, metabolic organization and metabolic flux during development to compensate for the effects of increasing fiber size. In the present study, we examined the impact of intracellular metabolite diffusive flux on the rate of postcontractile arginine phosphate (AP) resynthesis in burst locomotor muscle from small and large animals. AP recovery was measured following burst exercise, and these data were compared to a mathematical reaction‐diffusion model of aerobic metabolism. The measured rates of AP resynthesis were independent of fiber size, while simulations of aerobic AP resynthesis yielded lower rates in large fibers. These contradictory findings are consistent with previous observations that there is an increased reliance on anaerobic metabolism for post-contractile metabolic recovery in large fibers. However, the model results suggest that the interaction between mitochondrial ATP production rates, ATP consumption rates and diffusion distances yield a system that is not particularly close to being limited by intracellular metabolite diffusion. We conclude that fiber SA:V and O2 flux exert more control than intracellular metabolite diffusive flux over the developmental changes in metabolic organization and metabolic fluxes that characterize these muscles.
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TL;DR: Comparison of the model with experimental data from a wide range of skeletal muscle types reveals that most muscle fibers are not substantially limited by diffusion, but many are on the brink of rather substantial diffusion limitation.
15 citations
TL;DR: Some characteristics of the muscles of notothenioids have an apparent phylogenetic component while others seem to be adaptations to low temperature, and volume density is the only means of overcoming thermal constraints on oxidative capacity.
Abstract: Fish skeletal muscle is an excellent model for studying muscle structure and function, since it has a very well-structured arrangement with different fiber types segregated in the axial and pectoral fin muscles. The morphological and physiological characteristics of the different muscle fiber types have been studied in several teleost species. In fish muscle, fiber number and size varies with the species considered, limiting fish maximum final length due to constraints in metabolites and oxygen diffusion. In this work, we analyze some special characteristics of the skeletal muscle of the suborder Notothenioidei. They experienced an impressive radiation inside Antarctic waters, a stable and cold environment that could account for some of their special characteristics. The number of muscle fibers is very low, 12,700–164,000, in comparison to 550,000–1,200,000 in Salmo salar of similar sizes. The size of the fibers is very large, reaching 600 μm in diameter, while for example Salmo salar of similar sizes have fibers of 220 μm maximum diameter. Evolutionary adjustment in cell cycle length for working at low temperature has been shown in Harpagifer antarcticus (111 h at 0°C), when compared to the closely related sub-Antarctic species Harpagifer bispinis (150 h at 5°C). Maximum muscle fiber number decreases towards the more derived notothenioids, a trend that is more related to phylogeny than to geographical distribution (and hence water temperature), with values as low as 3,600 in Harpagifer bispinis. Mitochondria volume density in slow muscles of notothenioids is very high (reaching 0.56) and since maximal rates of substrate oxidation by mitochondria is not enhanced, at least in demersal notothenioids, volume density is the only means of overcoming thermal constraints on oxidative capacity. In brief, some characteristics of the muscles of notothenioids have an apparent phylogenetic component while others seem to be adaptations to low temperature.
15 citations
Cites background from "Does intracellular metabolite diffu..."
...Therefore, excessive cell size reduces the capacity for critical oxidative metabolic processes (Egginton and Sidell 1989; Boyle et al. 2003; Johnston et al. 2003b; Kinsey et al. 2005)....
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TL;DR: Two LIM protein coding genes, a paxillin-like transcript (pax) and a muscle LIM protein (mlp) were relatively up-regulated in muscle of wet season crabs, and their comparative up-regulation is consistent with a remodelling of leg muscle for migration in the wet season.
Abstract: SUMMARY During their annual breeding migration the Christmas Island land crab Gecarcoidea natalis sustains locomotion aerobically for up to 12 h per day compared with just 10 min during the dry season when their muscles quickly become anaerobic. A seasonal transition to an endurance-muscle phenotype would thus seem essential for migrating crabs. The current study employed a gene discovery approach comparing two expressed sequence tag (EST) libraries, one each for leg muscle from dry (non-migrating) and wet season (migrating) crabs. The 14 most abundant transcripts differed in their representation between the two libraries. The abundances of transcripts of genes predicted to code for different proteins forming contractile muscle components, including actin, troponin and tropomyosin, were significantly different between seasons and thus between physiological states. The shift in the isoform composition of the contractile elements provided evidence for a switch from slow phasic (S1) to slow tonic (S2) fatigue-resistant muscle fibres. A tropomyosin ( tm ) transcript aligned with a tm isoform of lobster ( tmS2 ), and semi-quantitative RT-PCR confirmed this isoform to be more abundant in the migrating crab muscle. Two LIM protein coding genes, a paxillin-like transcript ( pax ) and a muscle LIM protein ( mlp ), were relatively up-regulated in muscle of wet season crabs. These proteins have a fundamental role in muscle development and reconstruction, and their comparative up-regulation is consistent with a remodelling of leg muscle for migration in the wet season. Such a transition would result in an increased representation of aerobic endurance-type fibres concomitant with the greater aerobic exercise capacity of the migrating red crabs.
11 citations
Cites background from "Does intracellular metabolite diffu..."
...Less is known about the plasticity of crustacean muscles and alterations in their properties (Govind and Kent, 1982; Govind et al., 1987; Mykles, 1997; Boyle et al., 2003; Johnson et al., 2004; Kinsey et al., 2005)....
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...THE JOURNAL OF EXPERIMENTAL BIOLOGY muscles can be a mixture of several different fibre types (e.g. Mellon, 1992; Boyle et al., 2003; Kinsey et al., 2005) as well as mixed phenotype fibres (e.g. Govind et al., 1987; Govind, 1992; Medler and Mykles, 2003; Medler et al., 2004; Perry et al., 2009)....
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...muscles can be a mixture of several different fibre types (e.g. Mellon, 1992; Boyle et al., 2003; Kinsey et al., 2005) as well as mixed phenotype fibres (e....
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01 Jan 2005
3 citations
TL;DR: It is predicted that muscle function would be preserved in B. nubilus during periods of low tide emersion, whereas environmental hypoxia events, which are increasing in frequency and duration as global climates change, have the potential to diminish functionality of their giant muscle fibers.
3 citations
References
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Book•
01 Jan 1984
TL;DR: The importance of animal size in animal function is discussed in this paper, where it is shown that physical laws are equally important, for they determine rates of diffusion and heat transfer, transfer of force and momentum, strength of structures, the dynamics of locomotion, and other aspects of the functioning of animal bodies.
Abstract: This book is about the importance of animal size. We tend to think of animal function in chemical terms and talk of water, salts, proteins, enzymes, oxygen, energy, and so on. We should not forget, however, that physical laws are equally important, for they determine rates of diffusion and heat transfer, transfer of force and momentum, the strength of structures, the dynamics of locomotion, and other aspects of the functioning of animal bodies. Physical laws provide possibilities and opportunities for an organism, yet they also impose constraints, setting limits to what is physically possible. This book aims to give an understanding of these rules because of their profound implications when we deal with animals of widely different size and scale. The reader will find that the book raises many questions. Remarkable and puzzling information makes it read a little like a detective story, but the last chapter, instead of giving the final solution, neither answers all questions nor provides one great unifying principle.
2,736 citations
1,940 citations
"Does intracellular metabolite diffu..." refers background in this paper
...The intracellular diffusive flux of high-energy phosphates is largely mediated by phosphagen kinases, such as creatine kinase (CK) and arginine kinase (AK), although the mechanistic details are still the subject of study (reviewed by Walliman et al., 1992; Ellington, 2001)....
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TL;DR: Phosphocreatine content was measured by phosphorus nuclear magnetic resonance spectroscopy in the gastrocnemius muscles of pentobarbital-anesthetized rats during and after twitch stimulation to be consistent with a simple first-order electrical analog model of oxidative metabolism that is applicable at submaximal oxidative rates.
Abstract: Phosphocreatine (PCr) content was measured by phosphorus nuclear magnetic resonance spectroscopy in the gastrocnemius muscles of pentobarbital-anesthetized rats during and after twitch stimulation at rates up to 0.75 Hz. The monoexponential time constant for PCr changes was similar at the onset of vs. during recovery after stimulation and was not significantly different for different stimulation rates (mean time constant 1.44 min). Steady-state PCr level during stimulation was linearly related to the product of stimulation rate times peak twitch force. These results are shown to be consistent with a simple first-order electrical analog model of oxidative metabolism that is applicable at submaximal oxidative rates. The model assumes equilibrium of the creatine kinase reaction, which is modeled as a chemical capacitor, with capacitance proportional to the total creatine level, and PCr level proportional to the cytosolic free energy of ATP hydrolysis.
504 citations
"Does intracellular metabolite diffu..." refers methods in this paper
...This approach has been effectively employed to describe some of the major processes of energy metabolism in muscle, and a variety of kinetic models have been developed that closely match experimental data (e.g. Meyer, 1988; Jeneson et al., 1995; Vicini and Kushmerick, 2000; Korzeniewski, 2003)....
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TL;DR: Experimental results demonstrating the transport aspects of the CK reaction emphasize only one feature of a more general notion of facilitated diffusion by near-equilibrium metabolic reactions and do not per se establish the existence of any physical or functional compartmentation of ATP, ADP, PCr, or creatine.
Abstract: The diffusive mobility of solutes chemically connected by reversible reactions in cells is analyzed as a problem of facilitated diffusion. By this term we mean that the diffusive flux of any substance, X, which is in one metabolic pathway, is effectively increased when it participates in a second and equilibrium reaction with another substance Y because the total flux of X in the pathway is the sum of the fluxes of X and Y. This notion is generalized and is seen to include the familiar enhanced intracellular diffusion of oxygen by oxymyoglobin. In this framework the function of creatine kinase (CK) is seen to have two aspects: 1) phosphocreatine (PCr) via the CK reaction buffers the cellular ATP and ADP concentrations and 2) transport of high-energy phosphates is predominantly in the chemical form of PCr. This predominance of PCr is a consequence of the maintained ATP, ADP, and total creatine levels and of the apparent equilibrium constant of the reaction. Thus experimental results demonstrating the transport aspects of the CK reaction emphasize only one feature of a more general notion of facilitated diffusion by near-equilibrium metabolic reactions and do not per se establish the existence of any physical or functional compartmentation of ATP, ADP, PCr, or creatine. PCr can be a large source for increasing inorganic phosphate levels during contractile activity, possibly as a metabolic regulator. Neither the transport nor buffer aspects can be quantitatively important in cells with small distances between ATP-utilizing and ATP-generating sites, such as is the case with cardiac myofibrils and mitochondria.
497 citations
"Does intracellular metabolite diffu..." refers background or methods in this paper
...These are likely to include systems with relatively high rates of ATP production/consumption and distant sites of ATP utilization, such as in some muscle fibers with a higher aerobic capacity than examined here (Meyer et al., 1984; Stokes and Josephson, 1992; Vendelin et al., 2000; Saks et al., 2003; Suarez, 2003) or in the flagellum of spermatozoa, which has been the subject of many reaction–diffusion analyses (e....
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...…metabolism found theoretical evidence for concentration gradients in high-energy phosphate molecules during steady-state contraction in muscle (Mainwood and Rakusan, 1982; Meyer et al., 1984; Hubley et al., 1997; Aliev and Saks, 1997; Kemp et al., 1998; Vendelin et al., 2000; Saks et al., 2003)....
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...The mitochondrial boundary conditions at x=0 balance the fluxes of ATP and ADP into the bulk phase with the rates of formation and consumption at the mitochondria and are modeled using Michaelis-Menten kinetics with ADP activation (Meyer et al., 1984):...
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...A Km,mito value for ADP of 20·µmol·l–1 was used, which is within the range for fast skeletal muscle (Meyer et al., 1984)....
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...…the bulk phase with the rates of formation and consumption at the mitochondria and are modeled using Michaelis-Menten kinetics with ADP activation (Meyer et al., 1984): where RmitoATP and RmitoADP are the boundary reaction rates for ATP and ADP, respectively, Vm,mito is the maximal velocity…...
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TL;DR: It is hypothesized that the capacity for intracellular targeting of CK evolved early as a means of facilitating energy transport in highly polarized cells and was subsequently exploited for temporal ATP buffering and dynamic roles in metabolic regulation in cells displaying high and variable rates of aerobic energy production.
Abstract: Phosphagens are phosphorylated guanidino compounds that are linked to energy state and ATP hydrolysis by corresponding phosphagen kinase reactions: phosphagen + MgADP + H(+) guanidine acceptor + MgATP. Eight different phosphagens (and corresponding phosphagen kinases) are found in the animal kingdom distributed along distinct phylogenetic lines. By far, the creatine phosphate/creatine kinase (CP/CK) system, which is found in the vertebrates and is widely distributed throughout the lower chordates and invertebrates, is the most extensively studied phosphagen system. Phosphagen kinase reactions function in temporal ATP buffering, in regulating inorganic phosphate (Pi) levels, which impacts glycogenolysis and proton buffering, and in intracellular energy transport. Phosphagen kinase reactions show differences in thermodynamic poise, and the phosphagens themselves differ in terms of certain physical properties including intrinsic diffusivity. This review evaluates the distribution of phosphagen systems and tissue-specific expression of certain phosphagens in an evolutionary and functional context. The role of phosphagens in regulation of intracellular Pi levels likely evolved early. Thermodynamic poise of the phosphagen kinase reaction profoundly impacts this capacity. Furthermore, it is hypothesized that the capacity for intracellular targeting of CK evolved early as a means of facilitating energy transport in highly polarized cells and was subsequently exploited for temporal ATP buffering and dynamic roles in metabolic regulation in cells displaying high and variable rates of aerobic energy production.
472 citations
"Does intracellular metabolite diffu..." refers background in this paper
...The intracellular diffusive flux of high-energy phosphates is largely mediated by phosphagen kinases, such as creatine kinase (CK) and arginine kinase (AK), although the mechanistic details are still the subject of study (reviewed by Walliman et al., 1992; Ellington, 2001)....
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