An electrophysiological analysis of the synthesis of acetylcholine in preganglionic nerve terminals.

1. An electrophysiological analysis has been made of the synthesis of acetylcholine (ACh) in the preganglionic nerve terminals of the isolated superior cervical ganglion of the guinea-pig. The mean amplitude of excitatory post-synaptic potentials recorded intracellularly was taken as a measure of the ACh output per impulse from the terminals of a preganglionic axon.2. Prolonged repetitive stimulation of the cervical sympathetic trunk at 10 and 20 Hz led to a decline in ACh output over the first 5-15 min and then a maintained output for periods of up to an hour. The mean level of maintained output was 0.4 of the peak initial output.3. The maintained level of output was shown to be equal to the rate of synthesis of new transmitter and was not dependent on the addition of choline (3 x 10(-5)M) to the fluid in the organ bath.4. The ACh output per minute was shown to be directly proportional to the frequency of stimulation.5. A model has been proposed of the storage and synthesis of ACh in preganglionic nerve terminals during prolonged stimulation, in which choline from the hydrolysis of released ACh is the main source of substrate for synthesis of new transmitter, and the rate at which synthesis proceeds is controlled by the rate at which transmitter is released.