Release of Acetylcholine from a Nerve Terminal by Electric Pulses of Variable Strength and Duration

Abstract

IT has recently been shown¹ that the release of acetylcholine from a motor nerve ending does not occur immediately when the action potential arrives at the terminal, but starts after a delay of about 0.5 msec at 20° C (and considerably later at lower temperatures²). To find out more about the relation between the electrical changes in the nerve ending and the subsequent secretion of the transmitter substance, it is desirable to apply graded electric pulses locally to the presynaptic terminal. This has been difficult to achieve because above a certain strength a locally applied depolarizing pulse initiates an all-or-none impulse in the terminal³. To overcome this difficulty we have used the substance tetrodotoxin which is known to abolish impulses in nerve and muscle fibres without blocking the depolarizing action of acetylcholine on the end-plate⁴. Quite recently, Elmqvist and Feldman⁵ showed that the spontaneous miniature end-plate potentials (m.e.p.p.'s)—which are indicative of an intermittent spontaneous secretion of packets of acetylcholine from the terminals⁶—are not affected by tetrodo-toxin, and that their frequency can be raised, much as in a normal preparation, by increasing the external potassium concentration. Thus, tetrodo-toxin has the remarkable property, unlike other blocking agents such as curare or procaine, of paralysing the nerve and muscle fibre while leaving the special properties of the neuromuscular junction unimpaired.