Quantal acetylcholine release: vesicle fusion or intramembrane particles?

Images of vesicle openings in the presynaptic membrane have regularly been shown to increase in number after stimulation of cholinergic nerves. However, with a very few exceptions, the occurrence of vesicle openings is delayed in time with respect to the precise moment of transmitter release. In contrast, a transient change in the size and distribution of intramembrane particles (IMPs) has constantly been found as a characteristic change affecting the presynaptic membrane in a strict time coincidence with the release of acetylcholine quanta. This is illustrated here in a rapid-freezing experiment performed on small specimens of the Torpedo electric organ during transmission of a single nerve impulse. A marked change affected IMPs in the presynaptic membrane for 3-4 ms, i.e., a population of IMPs larger than 10 nm momentarily occurred in coincidence with the passage of the impulse. The nicotinic receptors, abundantly visible in the postsynaptic membranes, also underwent very fleeting structural changes during synaptic transmission. In conclusion, for rapidly operating neurotransmitters like acetylcholine, a characteristic IMP change was regularly found to coincide in the presynaptic membrane with the production of neurotransmitter quanta, whereas images of vesicles fusion were either delayed or even dissociated from the release process. This is discussed in connection to the different modes of release recently described for other secreting systems.