LAUSR

The objective of this article is to provide an historical perspective on a review of "Heat production and chemical change in muscle" written by Roger C. Woledge and published in Progress in Biophysics and Molecular Biology 50 years ago. We first provide a brief but broad summary of the history of muscle chemistry prior to 1971 and then to address the central theme of the 1971 review - that of energy balance. Energy balance is a method to establish whether all the energetically significant biochemical reactions accompanying muscle contraction have been identified. Woledge adopted the method was to compare the measured enthalpy output (i.e., the sum of the heat output and work output) to that expected from the extent of known biochemical reactions. Prior work had suggested that the observed and expected enthalpy outputs were similar but Woledge proposed that the expected heat had been overestimated and that, hence, there must be an unidentified reaction that accounted for as much as half the heat produced by a contracting muscle. We describe investigations carried out after the review that vindicated that view, ultimately characterising the processes producing the unexplained enthalpy which, in turn, led to identification of the hitherto unknown reaction. Those experiments and a more recent resurrection of the approach using fluorescent probes to monitor ATP turnover have now accounted for the processes that underlie the complex time courses of muscle heat production and ATP turnover during contraction, at least in the classical frog sartorius muscle preparation. However, the few studies performed on mammalian muscles since then have produced results that are difficult to reconcile with the ideas derived from energy balance studies of amphibian and fish muscles, thereby suggesting a new objective for energy balance studies.