Muscle heat: a window into the thermodynamics of a molecular machine

Abstract

contraction of muscle is characterized by the development of force and movement (mechanics) together with the generation of heat (metabolism). Heat represents that component of the enthalpy of ATP hydrolysis that is not captured by the microscopic machinery of the cell for the performance of work. It arises from two conceptually and temporally distinct sources: initial metabolism and recovery metabolism. Initial metabolism comprises the hydrolysis of ATP and its rapid regeneration by hydrolysis of phosphocreatine (PCr) in the processes underlying excitation-contraction coupling and subsequent cross-bridge cycling and sliding of the contractile filaments. Recovery metabolism describes those process, both aerobic (mitochondrial) and anaerobic (cytoplasmic), that produce ATP, thereby allowing the regeneration of PCr from its hydrolysis products. An equivalent partitioning of muscle heat production is often invoked by muscle physiologists. In this formulation, total enthalpy expenditure is separated into external mechanical work (W) and heat (Q). Heat is again partitioned into three conceptually distinct components: basal, activation, and force dependent. In the following mini-review, we trace the development of these ideas in parallel with the development of measurement techniques for separating the various thermal components.Microcalorimetry; muscle heat production; myothermy; thermopiles MUSCLE IS A MOLECULAR machine. It operates isothermally, isobarically, and isovolumetrically. At the microscopic level, it directly converts the Free Energy component of the enthalpy of ATP hydrolysis into cyclic attachment and detachment of actomyosin cross bridges, together with transportation of ions up their electrochemical potential gradients. At the macroscopic level, two consequences result: the generation of force and the evolution of heat. Of these two entities, heat is by far the more difficult to quantify and to interpret. In this brief review, we trace the development of techniques to measure muscle heat production from the mid-19th century to the present, providing parallel commentary on the progressive understanding of muscle function. We give particular consideration to the development of techniques of separating the metabolic cost of cross-bridge cycling from the purely "overhead" cost of its activation.

Experimental and modelling evidence of shortening heat in cardiac muscle

“…Previously, the omission of a shortening heat component meant that all cross‐bridge‐related heat was grouped under one label, Q XB (Loiselle et al . , b). However, the introduction of a shortening heat Q XB(Short) component allows Q XB to be further subdivided.…”

Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice

“…Although BAT is known to generate heat through NST (UCP1-dependent uncoupling) (2, 30 -33), some studies have questioned whether muscle has the ability to generate heat through NST (34). Other studies suggest a potential role for skeletal muscle in NST in human and animal models (18,(35)(36)(37)(38)(39)(40). Nedergaard and co-workers argue (34,41) that increased shivering is the only mechanism for cold adaptation in UCP1 Ϫ/Ϫ mice and questioned the existence of muscle-based NST.…”

Metabolic Cost of Activation and Mechanical Efficiency of Mouse Soleus Muscle Fiber Bundles During Repetitive Concentric and Eccentric Contractions

“…Similar to previous studies, we define muscle’s baseline-subtracted mechanical efficiency as the net mechanical work done divided by the total metabolic energy expenditure minus the metabolic energy expenditure during rest. At the single muscle level, both baseline-subtracted mechanical efficiency (for reviews, see: Woledge et al, 1985; Smith et al, 2005) and the relative contribution of the activation process to metabolic energy consumption (for reviews, see Barclay et al, 2007; Loiselle et al, 2016) have been extensively studied in poikilothermic animals, and to a lesser extent in mammals, the latter being more relevant to our understanding of human locomotion. In the study of mammalian muscle’s mechanical efficiency at the single muscle level, a distinction is usually made between the “initial” efficiency and “net” efficiency.…”

“…Under the assumption that the energy required to phosphorylate creatine is independent of the process for which ATP is used (i.e., the efficiency of the recovery process is invariant), the fraction of metabolic energy required for muscle (de)activation is the same when quantified using either initial or net metabolic energy expenditure. Using a variety of methods, the latter fraction has been estimated to be between 0.30 and 0.40 during short duration (<1 s) isometric contractions (Barclay et al, 2007; Loiselle et al, 2016). These results show that the metabolic energetic expenditure associated with (de)activation of muscle may be substantial.…”