The Croonian Lecture, 1967: The activation of striated muscle and its mechanical response

Since the end of the 1939-45 war, the task of someone trying to understand muscular contraction has become in some respects easier, and in others more difficult. On the credit side, straightforward explanations are now available—and well established—for the main events in neuromuscular transmission, propagation of the action potential, the inward spread of an activating process, chemical activation of the myofibrils, and the sliding filament process of length change. On the other side new properties, new structures and new substances have turned up which cannot yet be fitted into any comprehensive scheme. Further, we are still totally in the dark about the actual molecular processes involved even in those steps for which clear explanations are available at the electrophysiological or electronmicroscopical level. Yet another complication is the extraordinary variety of muscle types that are being discovered, even among such thoroughly studied groups of animals as amphibians and mammals. I have been repeatedly struck by cases where the investigation of muscle has been held up by a false assumption based on the supposition that different kinds of contractile materials must work in the same way. For example, it has often been argued that smooth muscle and striated muscle are essentially similar, and therefore the striations are of only minor importance; this argument was given, for example, by Bernstein (1901, p. 284). The still more general argument that the nature of the ‘contractility’ of muscle should be looked for in the supposedly simpler processes of protoplasmic movement had been the main theme of a book by Verworn (1892). This attitude was, I am sure, one of the main reasons for the almost complete disregard of the striations by physiologists and biochemists between about 1910 and 1950. Again, the elucidation of the slow motor system of certain striated muscle fibres, present in probably all vertebrates, was delayed for many years by the discovery that in mammals even the slow postural activity of limb and trunk muscles is accompanied by propagated action potentials characteristic of fast motor systems. It was widely assumed on this basis that ‘tonic’ contractions in all vertebrate striated muscles consisted of asynchronous twitches or unfused tetani in scattered motor units, and most physiologists came to disregard the numerous indications—physiological and pharmacological (Langley 1913; Sommerkamp 1928; Wachholder & von Ledebur 1930) as well as histological (see Krüger (1952) for references both to his own work in the thirties and to other work)—of the existence of a second, slow, system in skeletal muscles of the frog. The very slow contractions elicited in the familiar gastrocnemius muscle of the frog by stimulating small-diameter motor-nerve fibres (Tasaki & Kano 1942; Tasaki & Mizutani 1944; Tasaki & Tsukagoshi 1944) came as a complete surprise to most physiologists, and received little attention until the matter was taken up by Kufiler and his colleagues (e.g. Kuffler & Vaughan Williams 1953). The astonishing range of structural diversity that becomes apparent when one looks at the arthropods as well as the vertebrates has recently been emphasized by Hoyle (1967).