Nancy A. Curtin

The effect of the performance of work on total energy output and metabolism during muscular contraction

1. The production of heat (h) and work (w) and the changes in phosphocreatine (PCr) and ATP have been measured on tetanized isolated frog muscles (unpoisoned and in oxygen at 0° C) during shortening at constant velocity and during isometric contraction (both without relaxation). The former type of contraction was designed to maximize the fraction w/(h + w); the latter to minimize it.

Energy turnover for Ca2+ cycling in skeletal muscle.

The majority of energy consumed by contracting muscle can be accounted for by two ATP-dependent processes, cross-bridge cycling and Ca2+ cycling. The energy for Ca2+ cycling is necessary for contraction but is an overhead cost, energy that cannot be converted into mechanical work. Measurement of the energy used for Ca2+ cycling also provides a means of determining the total Ca2+ released from the sarcoplasmic reticulum into the sarcoplasm during a contraction. To make such a measurement requires a method to selectively inhibit cross-bridge cycling without altering Ca2+ cycling. In this review, we provide a critical analysis of the methods used to partition skeletal muscle energy consumption between cross-bridge and non-cross-bridge processes and present a summary of data for a wide range of skeletal muscles. It is striking that the cost of Ca2+ cycling is almost the same, 30–40% of the total cost of isometric contraction, for most muscles studied despite differences in muscle contractile properties, experimental conditions, techniques used to measure energy cost and to partition energy use and in absolute rates of energy use. This fraction increases with temperature for amphibian or fish muscle. Fewer data are available for mammalian muscle but most values are similar to those for amphibian muscle. For mammalian muscles there are no obvious effects of animal size, muscle fibre type or temperature.

Energy storage during stretch of active single fibres from frog skeletal muscle

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 μm). 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.

Inferring crossbridge properties from skeletal muscle energetics

Work is generated in muscle by myosin crossbridges during their interaction with the actin filament. The energy from which the work is produced is the free energy change of ATP hydrolysis and efficiency quantifies the fraction of the energy supplied that is converted into work. The purpose of this review is to compare the efficiency of frog skeletal muscle determined from measurements of work output and either heat production or chemical breakdown with the work produced per crossbridge cycle predicted on the basis of the mechanical responses of contracting muscle to rapid length perturbations. We review the literature to establish the likely maximum crossbridge efficiency for frog skeletal muscle (0.4) and, using this value, calculate the maximum work a crossbridge can perform in a single attachment to actin (33 x 10(-21) J). To see whether this amount of work is consistent with our understanding of crossbridge mechanics, we examine measurements of the force responses of frog muscle to fast length perturbations and, taking account of filament compliance, determine the crossbridge force-extension relationship and the velocity dependences of the fraction of crossbridges attached and average crossbridge strain. These data are used in combination with a Huxley-Simmons-type model of the thermodynamics of the attached crossbridge to determine whether this type of model can adequately account for the observed muscle efficiency. Although it is apparent that there are still deficiencies in our understanding of how to accurately model some aspects of ensemble crossbridge behaviour, this comparison shows that crossbridge energetics are consistent with known crossbridge properties.

Temperature change as a probe of muscle crossbridge kinetics: a review and discussion

Following the ideas introduced by Huxley (Huxley 1957, Prog. Biophys. Biophys. Chem. 7, 255–318), it is generally supposed that muscle contraction is produced by temporary links, called crossbridges, between myosin and actin filaments, which form and break in a cyclic process driven by ATP splitting. Here we consider the interaction of the energy in the crossbridge, in its various states, and the force exerted. We discuss experiments in which the mechanical state of the crossbridge is changed by imposed movement and the energetic consequence observed as heat output and the converse experiments in which the energy content is changed by altering temperature and the mechanical consequences are observed. The thermodynamic relationship between the experiments is explained and, at the first sight, the relationship between the results of these two types of experiment appears paradoxical. However, we describe here how both of them can be explained by a model in which mechanical and energetic changes in the crossbridges occur in separate steps in a branching cycle.

Muscle directly meets the vast power demands in agile lizards

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 lizards muscle fibres alone; there is no need for mechanical power amplifying mechanisms.

Is the efficiency of mammalian (mouse) skeletal muscle temperature dependent

Myosin crossbridges in muscle convert chemical energy into mechanical energy. Reported values for crossbridge efficiency in human muscles are high compared to values measured in vitro using muscles of other mammalian species. Most in vitro muscle experiments have been performed at temperatures lower than mammalian physiological temperature, raising the possibility that human efficiency values are higher than those of isolated preparations because efficiency is temperature dependent. The aim of this study was to determine the effect of temperature on the efficiency of isolated mammalian (mouse) muscle. Measurements were made of the power output and heat production of bundles of muscle fibres from the fast‐twitch extensor digitorum longus (EDL) and slow‐twitch soleus muscles during isovelocity shortening. Mechanical efficiency was defined as the ratio of power output to rate of enthalpy output, where rate of enthalpy output was the sum of the power output and rate of heat output. Experiments were performed at 20, 25 and 30°C. Maximum efficiency of EDL muscles was independent of temperature; the highest value was 0.31 ± 0.01 (n= 5) at 30°C. Maximum efficiency of soleus preparations was slightly but significantly higher at 25 and 30°C than at 20°C; the maximum mean value was 0.48 ± 0.02 (n= 7) at 25°C. It was concluded that maximum mechanical efficiency of isolated mouse muscle was little affected by temperature between 20 and 30°C and that it is unlikely that differences in temperature account for the relatively high efficiency of human muscle in vivo compared to isolated mammalian muscles.

The energetic cost of activation in mouse fast‐twitch muscle is the same whether measured using reduced filament overlap or N‐benzyl‐p‐toluenesulphonamide

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 (EA), 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 EA measured by inhibiting force generation by: (1) the conventional method of reducing contractile filament overlap; and (2) pharmacological inhibition using BTS.

Actomyosin energy turnover declines while force remains constant during isometric muscle contraction

Energy turnover was measured during isometric contractions of intact and Triton‐permeabilized white fibres from dogfish (Scyliorhinus canicula) at 12°C. Heat + work from actomyosin in intact fibres was determined from the dependence of heat + work output on filament overlap. Inorganic phosphate (Pi) release by permeabilized fibres was recorded using the fluorescent protein MDCC‐PBP, N‐(2‐[1‐maleimidyl]ethyl)‐7‐diethylamino‐coumarin‐3 carboxamide phosphate binding protein. The steady‐state ADP release rate was measured using a linked enzyme assay. The rates decreased five‐fold during contraction in both intact and permeabilized fibres. In intact fibres the rate of heat + work output by actomyosin decreased from 134 ±s.e.m. 28 μW mg−1 (n= 17) at 0.055 s to 42% of this value at 0.25 s, and to 20% at 3.5 s. The force remained constant between 0.25 and 3.5 s. Similarly in permeabilized fibres the Pi release rate decreased from 5.00 ± 0.39 mmol l−1 s−1 at 0.055 s to 39% of this value at 0.25 s and to 19% at 0.5 s. The steady‐state ADP release rate at 15 s was 21% of the Pi rate at 0.055 s. Using a single set of rate constants, the time courses of force, heat + work and Pi release were described by an actomyosin model that took account of the transition from the initial state (rest or rigor) to the contracting state, shortening and the consequent work against series elasticity, and reaction heats. The model suggests that increasing Pi concentration slows the cycle in intact fibres, and that changes in ATP and ADP slow the cycle in permeabilized fibres.

A comparison of the energy balance in two successive isometric tetani of frog muscle

1. Measurements were made of the energy produced as heat and work (h + w) and the chemical changes which occurred between the beginning and end of each of two periods of stimulation. The muscles contracted tetanically under isometric conditions. Each period of stimulation (tetanus) lasted 5 sec and there was an interval of 3 sec between them. The tension developed in the second tetanus was 91% of that in the first.