Is the MEPP due to the release of one vesicle or to the simultaneous release of several vesicles at one active zone?

Miniature end-plate potentials (MEPPs) recorded at the neuromuscular junction were initially reported to be normally distributed and have been attributed to quantal ACh release. This quantum was later correlated with the release of the content of one clear vesicle. This is the 'classical vesicular hypothesis'. Recent observations of subminiature end-plate potentials (s-MEPPs) and of multimodal distribution of the MEPP amplitudes have led to the formulation of a new 'multivesicular hypothesis'. It attributes the s-MEPP to the release of one vesicle and the MEPP to the simultaneous release of several vesicles at one active zone. The distribution of MEPP intervals, the evaluation of the ACh content of a vesicle and of the ACh necessary to produce a MEPP, estimates of the number of vesicles missing following repeated stimulation, and the freeze fracture studies of the active zone do not permit a definitive rejection of either hypotheses.