The relationship between the nerve terminal action potential and transmitter release from sympathetic postganglionic nerve terminals has been studied in vitro by focal extracellular recording. 2. In the absence of stimulation, 'spontaneous excitatory junction currents' (SEJCs) were recorded with amplitudes up to 500 microV, durations of 50-80 ms and frequencies of occurrence of 0.3-0.05 Hz; SEJCs of unusually long time course were also observed. The SEJCs were not recorded in tissues pre-treated with 6-hydroxydopamine to destroy sympathetic nerves, were unaffected by tetrodotoxin (TTX), the competitive alpha-adrenoceptor antagonists, prazosin and phentolamine, the irreversible alpha-adrenoceptor antagonist benextramine but were blocked by alpha,beta-methylene ATP which desensitizes P2-purinoceptors. 3. During trains of supramaximal stimuli at 0.1-4 Hz stimulus locked 'excitatory junction currents' (EJCs) were evoked intermittently from the population of varicosities located under the suction electrode with a probability of occurrence of 0.005-0.8. Although EJCs occurred intermittently, they were always preceded by an associated, non-intermittent, nerve impulse (delay less than or equal to 3 ms). 4. The EJCs reflect transmitter release from nerves because they were abolished by TTX, removal of calcium from the bathing medium, exposure to alpha-beta-methylene ATP and exhibited frequency-dependent facilitation. 5. Amplitude distributions of SEJCs and EJCs recorded in the same attachment were similar and skewed towards low-amplitude events. Individual SEJCs and EJCs could be found which were identical in amplitude and time course. 6. Locally applied TTX blocked impulse propagation and transmitter release in the terminal region; electrotonic invasion of the terminals from the point of block did not activate the transmitter release process. 7. These studies indicate that (1) intermittence of transmitter release is caused by a low probability of release in the invaded varicosity and is not caused by conduction failure in the terminal regions, (2) only a single quantum is normally secreted when the release mechanism of a varicosity is activated by the nerve impulse and (3) active invasion of the terminals is necessary for transmitter release to occur.
