Transmitter release: prepackaging and random mechanism or dynamic and deterministic process.

Abstract

Stepwise variations in end-plate potential amplitudes that are also multiples of spontaneous miniature end-plate potentials (MEPPs) demonstrate a quantal nature of evoked transmitter release at the vertebrate neuromuscular junction. Both the number of quanta which form relatively small end-plate potentials (EPPs) and the time intervals between MEPPs were found to fit Poisson statistics. These observations suggested that the release process randomly liberates uniform quantities of transmitter. Initial studies showed that quantal size remained stable after seemingly high rates of release which was interpreted to indicate that a large store of equally sized, equally available, and independently releasable quanta are present in the nerve terminals. The observation of numerous presynaptic vesicles that contain transmitter provided a morphological basis for prepacked transmitter (i.e., quanta). However, physiological studies over the last 15 years have yielded data that are difficult to incorporate into the quantum-vesicle hypothesis. With normal conditions and during most treatments which increase the rate of release, two classes of MEPPs have been found and both show a substructure. The bell-MEPP class was characterized by Fatt and Katz and the smaller skew-MEPP class has been studied by Kriebel. The ratio of the two classes and substructure compositions of both classes are variable. Short series of MEPPs and unitary EPPs (U-EPPs) show preferred amplitudes and longer series of MEPPs and U-EPPs show stepwise variations in amplitude. Slow-MEPPs and giant MEPPs belong to the skew class and represent nearly synchronous bursts of smaller MEPPs. Transmitter packet formation, preferred amplitudes, stepwise variations in amplitudes, random-like distributions and organized bursts can be simulated by a simple deterministic system, the drop formation process, that is known for its periodic and chaotic behaviors which are determined by the single parameter of flow rate. MEPP intervals, sizes and classes, are also dependent on rates of release which demonstrate that the release process(es) is highly organized and sensitive to different conditions. We demonstrate that the processes of drop formation and release of a packet of transmitter have similar properties and that deterministic characteristics describe MEPP and U-EPP time dependencies and amplitude substructures. The data and model presented here suggest that packet size of acetylcholine may be determined at the moment of release.