[Neurotransmitter release: a process of membrane fusion occurring in fractions of milliseconds]

The physiological mechanisms involved in neurotransmitter release were established thanks to the pioneer work of Katz, Del Castillo and Miledi at the neuromuscular junction. They termed their work as the quantal hypothesis of synaptic transmission. This hypothesis was further established morphologically by the work of Heuser and Reese. However, the molecular events underlying this process are poorly understood. We are starting to know which proteins interact between the vesicle and plasma membrane to promote fusion and to identify which molecules participate in the sensing of cytosolic calcium.

Thanks to the combination of molecular biology, electrophysiology and microfluorometry, a huge amount of new information is been obtained on the mechanisms participating in synaptic transmission. This data deals with processes concerning to different pools of synaptic vesicles and their availability to reach the presynaptic membrane; the molecular events responsible for the targeting of these vesicles with the plasma membrane; the sensitivity to calcium at the presynaptic membrane; the fusion of membranes required to release the vesicle contents, and the mechanisms responsible for membrane retrieval needed for presynaptic homeostasis.

In this review we discuss new data regarding synaptic function. However, some key points are still a matter of controversy. Meanwhile the quantal hypothesis is valid, the precise processes by which channels and vesicles interact, membrane is recycled and vesicles reused are still controversial. New techniques should be developed to address these points.