Delay between fusion pore opening and peptide release from large dense-core vesicles in neuroendocrine cells.

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Abstract

Peptidergic neurotransmission is slow compared to that mediated by classical neurotransmitters. We have studied exocytotic membrane fusion and cargo release by simultaneous capacitance measurements and confocal imaging of single secretory vesicles in neuroendocrine cells. Depletion of the readily releasable pool (RRP) correlated with exocytosis of 10%-20% of the docked vesicles. Some remaining vesicles became releasable after recovery of RRP. Expansion of the fusion pore, seen as an increase in luminal pH, occurred after approximately 0.3 s, and peptide release was delayed by another 1-10 s. We conclude that (1) RRP refilling involves chemical modification of vesicles already in place, (2) the release of large neuropeptides via the fusion pore is negligible and only proceeds after complete fusion, and (3) sluggish peptidergic transmission reflects the time course of vesicle emptying.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Peptides/*metabolism, PC12 Cells, Neurosecretory Systems/cytology/*metabolism, Membrane Fusion/*physiology, Luminescent Proteins, Kinetics, Indicators and Reagents, Hydrogen-Ion Concentration, Exocytosis/*physiology, Fluorescence, Rats, Secretory Vesicles/*metabolism, Support, Non-U.S. Gov't, Electric Stimulation, Cell Line, Animal
Original languageEnglish
Pages (from-to)287-299
JournalNeuron
Volume33
Issue number2
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes