Changes in MEPP frequency during depression of evoked release at the frog neuromuscular junction

1. Endplate potentials (EPPs) and miniature endplate potentials (MEPPs) were recorded from frog neuromuscular junctions bathed in Ringer solutions containing normal (1.8 mM) or high (3.6 mM) Ca2+. The peptide toxin mu-conotoxin GIIIA was added to the Ringer solution to prevent muscle action potentials and contraction. 2. The nerve was stimulated with conditioning trains of 200-4800 impulses applied at 20 impulses s-1 to characterize the effects of repetitive stimulation on changes in EPP amplitude and MEPP frequency under high quantal conditions. 3. MEPP frequency was dramatically increased during and immediately following repetitive stimulation under high quantal conditions, whereas EPP amplitude was greatly depressed. There was no effect of repetitive stimulation on MEPP amplitude. 4. Following the conditioning stimulation the increase in MEPP frequency decayed back to the control level with a time course that could be described by four exponentials. The time constants of these exponentials were very similar to those that describe the components of stimulation-induced increases in EPP amplitude and MEPP frequency observed under low quantal conditions when depression is absent. 5. The results of this study indicate that depression and the components of stimulation-induced increases in release (facilitation, augmentation and potentiation) can be present at the same time, suggesting that the mechanism of depression involves different underlying factors from the mechanism(s) responsible for increases in release. They also indicate either that depression selectively affects only those quanta destined to be released in direct response to the nerve action potential, which would suggest that EPPs and MEPPs arise from different pools of transmitter, or that depression in some way affects a step in the release process involved only in evoked release, and not asynchronous (spontaneous) release.