The Croonian Lecture - The transmission of impulses from nerve to muscle, and the subcellular unit of synaptic action

The original intention of the founders of this Lectureship was to encourage the study of the physiological mechanism of ‘local motion’. To choose the neuromuscular junction as the subject of this lecture seemed therefore fitting enough. My purpose, however, is not to discuss the processes involved in the initiation of muscular movement, but rather to look at the properties of the junction as an example of a synapse, that is of a functional contact between two excitable cells. Now at first sight, the junction between motor nerve and the fast skeletal muscles of vertebrate animals could hardly be singled out as a worthy example of a synapse which deserves our special attention. Unlike its counterparts in arthropod muscle and unlike most synapses in our nerve centres, the skeletal nerve-muscle junction does not contribute to the integration of converging nerve messages. It merely serves as a point of passage in a non-stop process of signalling which takes its origin in the spinal cord and ends with immediate contraction of a large group of muscle fibres which are connected to the terminal branches of the axon. This unfailing type of response had made many physiologists inclined to believe that there was nothing to distinguish the operation of the neuromuscular junction from the mechanism by which the action potential wave travels down the nerve axon and then continues along the muscle fibre where it activates the contractile process. And yet, the object of this lecture is to show that not only is there a special mechanism of chemical mediation interposed between the two cells, but that the neuromuscular junction possesses, in a somewhat concealed form, the specific synaptic properties which are essential for the integration of converging and conflicting signals in our nerve centres. Conduction of impulses along nerve or muscle fibres depends on two main factors: on the continuity of the cable structure of the cell, and on an automatic mechanism of amplification which is built into the surface membrane and which serves to make up for the imperfections of the cable structure. The cable property is due to the presence of a thin cylindrical cell membrane of very low electric conductivity and can be represented by a circuit diagram as in figure 1. By itself, this property does not enable the fibres to conduct an electric signal over any length. A brief voltage pulse fed into the line at one point would lose most of its amplitude within a few millimetres. In fact, the insulation of the membrane and the conductance of the fibre core are not good enough to serve for long-distance communication. But when the potential across the membrane is displaced by a certain critical amount, the so-called threshold, the membrane potential becomes unstable. Electric energy is suddenly released and produces a large transient amplification of the initial potential change. The amplified signal is passed on by cable linkage to the next region of the fibre where it again triggers off the release of energy and boosts itself as soon as the threshold level is exceeded. In this way, the all-or-none response of nerve and muscle comes about and travels rapidly towards the end of the fibre without diminishing in amplitude.