An Electrophysiological Analysis of the Uptake of Noradrenaline at Sympathetic Nerve Terminals

1. An electrophysiological analysis has been made of the uptake of NAd in the sympathetic nerve terminals of the isolated vas deferens of the mouse. The amplitude of the excitatory junction potentials (e.j.p.s) recorded intracellularly in smooth muscle cells was taken as a measure of the NAd output per impulse from the terminals of sympathetic axons.2. Neuronal uptake blockers (desipramine and cocaine) greatly depressed the amplitude of all e.j.p.s after the first in a short train (< 100) at high frequencies (>/= 1 Hz).3. Blocking neuronal uptake did not affect the time course of decline in amplitude of the e.j.p. during long trains of stimulation over several minutes, apart from the immediate depression in the e.j.p. following the first few impulses.4. The time course of decline of the e.j.p. amplitude during continual stimulation, when both neuronal uptake and synthesis was blocked, was similar to that when only synthesis was blocked, apart from the immediate depression following the first few impulses.5. Phenoxybenzamine reversed the normal depression in e.j.p. amplitude observed at high frequencies (>/= 1 Hz) to facilitation. This facilitation lasted for several minutes of high frequency stimulation.6. A model has been proposed of the sympathetic nerve terminal, in which NAd is released by each nerve impulse in a train from a small pool in the nerve terminal, which is principally replenished by uptake of the NAd released by the immediately preceding impulses in the train. The pool is replenished to a less extent by transmitter located in two stores in the terminal which are in turn replenished by transmitter synthesis.