Muscular fatigue has been studied using 31PNMR to measure the levels and rates of utilisation of several key metabolites and the free-energy change for ATP hydrolysis. Force development is closely correlated with metabolite levels and is proportional to the rate at which ATP is hydrolysed.

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SUMMARY1. We have used phosphorus nuclear magnetic resonance (31P NMR) to study muscular fatigue in anaerobic amphibian muscle. In this paper the biochemical and energetic changes that result from a series of tetani are related to the decrease in rate constant (1/r) for the final, exponential, phase of relaxation.2. Using 31P NMR we have measured the concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and ATP as well as the internal pH. From our measurements we have calculated [creatine], [free ADP], the free-energy change (more precisely, the affinity A = -dG/dg) for ATP hydrolysis and the rates of lactic acid production and of ATP hydrolysis. 3. We have found that 1/, the rate constant of relaxation, is correlated with each of the following, independently of the pattern of stimulation: isometric force production, all of the measured or calculated metabolite levels, pH and dG/dg.4. There is a clear dependence upon the pattern of stimulation of the relation between 1/r and each of the following: total duration of the experiment, number of contractions, rate of lactic acid production and rate of ATP hydrolysis.5. The rate of relaxation is linearly related to [PCr], [creatine], [Pi] and dG/d6. It is nonlinearly related to isometric force, [ATP], [H+] and rate of ATP hydrolysis.6. We conclude that the change in 1/IT, like that of isometric force, depends upon metabolic factors, and not upon any independent changes in the activation or deactivation of contraction. We suggest that 1/ir may depend upon the free-energy change for ATP hydrolysis which in turn may be related to the rate of Ca2+ uptake into the sarcoplasmic reticulum.

The response of a muscle to stimulation is classically divided into two phases: contraction and relaxation. The mechanical properties of the muscle in the first phase have been extensively studied (for references, see Jewell & Wilkie, 1958) and much is known about the way in which tension is developed and work is done, but the second phase is much less clearly understood. A. V. Hill (1949b) defined relaxation simply in terms of the external mechanical changes in the muscle, as 'the process by which the muscle returns, after contraction, to its initial length or tension'.Originally our interest in relaxation was aroused by the marked difference between the time courses of isotonic and of isometric twitches. For instance, in Fig. 1, one is confronted by the apparently paradoxical situation that after having lifted a load of 3 g wt. the muscle has completely relaxed at a time when it could have borne tension of 5 g wt. under isometric conditions. Admittedly, with small loads like this, the situation is complicated by an additional factor, for in the isotonic case the muscle has shortened appreciably. However, even with large loads, where the isotonic shortening is much less, mechanical activity has apparently ended at a time when the isometrically contracting muscle is still capable of bearing a considerable tension. METHODSAll the experiments were performed on frogs' sartorii (English Rana temporaria), kept immersed in Ringer's solution (mM: NaCl 115-5; KCI 2-0; CaCl2 1-8; Na phosphate buffer, pH 7 0, 2.0) at 00 C. Isotonic or isometric recordings alone give an incomplete picture of the changes in the mechanical state of the muscle, so we decided to record length and tension changes simultaneously during various different types of contraction. The length changes were recorded in the usual way by connecting the muscle to a light lever, the movements of which were 'sensed' by a photo-electric arrangement (see Jewell & Wilkie, 1958 for further experimental details). In theory the tension in the muscle could have been measured simultaneously and directly in one of three ways: by attaching a suitable transducer to the pelvic muscle clamp; by incorporating a transducer in the connexion to the muscle; or by mounting a transducer at the tip of the lever. The mechano-electronic transducer, RCA 5734, which we normally use to measure tension, cannot conveniently be immersed in Ringer's solution; and to have mounted it at the tip of the lever would have produced an undesirably