Two mechanisms of synaptic vesicle recycling in rat brain nerve terminals

Michael A. Cousin*, Phillip J. Robinson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

KCl and 4-aminopyridine (4-AP) evoke glutamate release from rat brain cortical nerve terminals by voltage clamping or by Na+ channel-generated repetitive action potentials, respectively. Stimulation by 4-AP but not KCl is largely mediated by protein kinase C (PKC). To determine whether KCl and 4-AP utilise the same mechanism to release glutamate, we correlated glutamate release with release of the hydrophobic synaptic vesicle (SV) marker FM2-10. A strong correlation was observed for increasing concentrations of KCl and after application of phorbol 12-myristate 13-acetate (PMA) or staurosporine. The parallel increase in exocytosis measured by two approaches suggested it occurred by a PKC-independent mechanism involving complete fusion of SVs with the plasma membrane. At low concentrations of 4-AP, alone or with staurosporine, glutamate and FM2-10 release also correlated. However, higher concentrations of 4-AP or of 4-AP plus PMA greatly increased glutamate release but did not further increase FM2-10 release. This divergence suggests that 4-AP recruits an additional mechanism of release during strong stimulation that is PKC dependent and is superimposed upon the first mechanism. This second mechanism is characteristic of kiss-and-run, which is not detectable by styryl dyes. Our data suggest that glutamate release in nerve terminals occurs via two mechanisms: (1) complete SV fusion, which is PKC independent; and (2) a kiss-and-run-like mechanism, which is PKC dependent. Recruitment of a second release mechanism may be a widespread means to facilitate neurotransmitter release in central neurons.

Original languageEnglish
Pages (from-to)1645-1653
Number of pages9
JournalJournal of Neurochemistry
Volume75
Issue number4
DOIs
Publication statusPublished - 2000

Keywords / Materials (for Non-textual outputs)

  • Exocytosis
  • FM2-10
  • Glutamate release
  • Kiss-and-run
  • Protein kinase C
  • Styryl dyes

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