Light microscopy: sliding filament theory

Andrew Huxley switched from nerve to muscle research in 1951 immediately after completing the papers with Hodgkin on the squid giant axon. He later wrote, explaining the change: “For one thing I had never worked on anything but nerve, and for another, there was at that time (and indeed for a good many years after) no obvious way of pushing the analysis of excitation to a deeper level” (A. F. Huxley, 1977). Huxley's interest in muscle had been kindled when he took over the lectures on muscle to the final-year undergraduate students at Cambridge from David Hill (son of A. V. Hill, and himself a fine muscle physiologist). David Hill passed on his lecture notes, which included a description of some of the nineteenth-century observations of muscle using light microscopy. A number of authors had accurately described the appearance of striated muscle and the way in which the striations change during contraction, though there was a certain amount of conflict in the subsequent literature, particularly about which of the bands – the A-band or the I-band – changes in length when a muscle fibre is stretched or contracts (A. F. Huxley, 1977).

In 1951, knowledge of the structures underlying the striations was sketchy. It was thought that the muscle proteins actin and myosin existed as a complex that ran from end to end of a muscle, and theories of contraction involved a folding of this complex (e.g., Astbury, 1947). Early electron microscopy of muscle using longitudinal sections seemed to confirm this view, apparently showing that the filaments in the Aband and the I-band were continuous, though it was soon to be shown be shown that myosin was located in the A-band.