Single and multiple vesicle fusion induce different rates of endocytosis at a central synapse

• Published in: Nature (London) 2002-05, Vol.417 (6888), p.555-559
• Main Authors: SUN, Jian-Yuan, WU, Xin-Sheng, WU, Ling-Gang
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Biological and medical sciences; Brain Stem - cytology; Brain Stem - drug effects; Brain Stem - metabolism; Calcium - metabolism; Calcium - pharmacology; Cell physiology; Electric Capacitance; Endocytosis; Endocytosis - drug effects; Excitatory Postsynaptic Potentials; Exocytosis; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Kinetics; Membrane Fusion - drug effects; Membranes; Molecular and cellular biology; Neurology; Physiology; Rats; Rats, Wistar; Secretory Vesicles - drug effects; Secretory Vesicles - metabolism; short-term depression; Synapses - drug effects; Synapses - metabolism; Synaptic Transmission
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/417555a

During synaptic transmission, neurotransmitter-laden vesicles fuse with the presynaptic membrane and discharge their contents into the synaptic cleft. After fusion, the vesicular membrane is retrieved by endocytosis for reuse. This recycling mechanism ensures a constant supply of releasable vesicles at the nerve terminal. The kinetics of endocytosis have been measured mostly after intense or non-physiological stimulation. Here we use capacitance measurements to resolve the fusion and retrieval of single and multiple vesicles following mild physiological stimulation at a mammalian central synapse. The time constant of endocytosis after single vesicle fusion was 56 ms; after a single action potential or trains at < or = 2 Hz it was about 115 ms, but increased gradually to tens of seconds as the frequency and the number of action potentials increased. These results indicate that an increase in the rate of exocytosis at the active zone induces a decrease in the rate of endocytosis. Existing models, including inhibition of endocytosis by Ca(2+), could not account for these results our results suggest that an accumulation of unretrieved vesicles at the plasma membrane slows endocytosis. These findings may resolve the debate about the dependence of endocytosis kinetics on the stimulation frequency, and suggest a potential role of regulation of endocytosis in short-term synaptic depression.