The role of calcium in neuromuscular facilitation.

1. The hypothesis is put forward that a residue of the ;active calcium' which enters the terminal axon membrane during the nerve impulse is responsible for short-term facilitation.2. This suggestion has been tested on the myoneural junction by varying the local calcium concentration so that during the first of two nerve impulses Ca is either much lower than, or raised to a level approaching that, during the second impulse. Facilitation is much larger in the latter case, which is in accordance with the ;calcium hypothesis'.3. A short pulse of depolarization focally applied to the junction is followed by a brief period of very intense facilitation. This can be seen in the tetrodotoxin-treated preparation, e.g. by lengthening the depolarization from 1 to 2 msec which can cause a more than fifty-fold increase in transmitter release. This large ;early facilitation' (which presumably occurs also during the course of a normal action potential) is discussed in relation to the ;calcium hypothesis'.