SINCE. muscular contraction is initiated by a reduction in the magnitude of the resting membrane potential of the muscle fibre, the immediate function of the neuromuscular transmission process may be expected to be the alteration of the membrane-potential level. In those muscle fibres where the propagated action-potential mechanism is found, a single local depolarization of sufficient magnitude is all that is necessary to initiate contraction, although this must necessarily be of the stereotyped, all-or-nothing kind. In muscle fibres where propagated action potentials cannot be set up, the position is more complex. Also, in some muscles, or in some actions, it may be desirable to alter the membrane potential in a less explosive manner than is the case with the propagated action potential. We will deal for the time being only with the setting-up of propagative impulses in the typical, vertebrate, skeletal muscle fibre. Evidence regarding their initiation has been obtained, particularly with the aid of the South American Indian's arrow poison, curare. In very minute quantities curare effects a block in neuromuscular transmission. Neither the capacity of the nerves to transmit impulses nor the ability of the muscle fibres to propagate action potentials and respond to them by normal twitches are affected by the drug, as independent stimulation and recording from the nerve and muscle demonstrate. The block is confined to the neuromuscular junction. In a similar way it can be shown that the neuromuscular junction is also the principal site of fatigue when the muscle response declines after continued stimulation via the nerve.
Modern knowledge of the mechanism of neuromuscular transmission started to accumulate after Dale, Feldberg & Vogt ( 1936) had shown that when the motor nerves of the perfused