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

The 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.

Is relaxation an active process?

Measurements of muscle heat production had indicated that relaxation is not an active process. Experiments to test this conclusion were made in two ways: ( a ) by measuring the mechanical latent period in isometric contractions over a wide range of lengths down to less than half the natural length in the body, and ( b ) by determining the relation between resting tension and length down to lengths at which the muscle became slack. In a muscle under its resting tension alone the latent period after a shock remains nearly constant over a wide range of lengths. This range is extended by previous stimulation. If active relaxation occurred the latent period would be greatly increased. A resting muscle exerts measurable tension down to 60 to 75% of its natural length in the body. By previous stimulation at a shorter length the range of lengths within which measurable tension is exerted is increased. In a muscle under zero external load lengthening occurs after contraction only from very short lengths. It is attributed to an elastic restoring force set up by the lateral expansion of the fibres. The ' δ -state’ described by Ramsey & Street in isolated fibres allowed to shorten too much is discussed. It may be due to mechanical damage to internal structures normally reinforcing the sarcolemma against expansion. The nature of the contractile linkages in muscle is considered.

Methods of analysing the heat production of muscle

The initial heat production of muscle (as distinguished from the delayed heat production) occurs so rapidly that the determination of its distribution in time, particularly in relation to contraction, relaxation and the performance of mechanical work, requires special methods of analysis (see e.g. Hartree 1933). The only means hitherto found satisfactory of measuring muscle heat production has employed a thermopile and galvanometer. For the rise of temperature involved the e.m.f. developed by the thermopile is only a few microvolts, and it has not been possible to devise any really satisfactory method of amplification: the current has had to be read directly by the galvanometer. Since the current was small the galvanometer had to be sensitive, and therefore comparatively slow. This introduced the first element of delay in the measurement of the heat, that due to the galvanometer. The second was due to the thermopile, for all thermopiles hitherto employed have been rather slow in reaching the temperature of the muscle. Moreover, their heat capacity has been so large that the sensitivity of the system has been considerably less than that calculated simply from the constants of the apparatus. For all these reasons the analysis and the calibration have been performed by heating the muscle electrically during a known short interval, or “instantaneously”, and finding numerically what distribution of such heat-pulses would give the same deflexion, in time and amplitude, as the heat produced by the stimulated muscle. The method is laborious and there are various objections to it, particularly (i) the requirement that the muscle must be of uniform cross-section if it is to be uniformly heated (see Hill 19316, p. 144, Appendix II), (ii) the need of very good electrical insulation, in order to avoid leaks, and (iii) the danger of non-uniform heating in the immediate neighbourhood of the electrodes leading current to the muscle. Within limits, however, the method has fulfilled its purpose, and all significant results on the time-course of the heat production of muscle (and nerve) have been obtained with it.