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J Neurosci. 2011 Nov 9;31(45):16318-26. doi: 10.1523/JNEUROSCI.3358-11.2011.

Ca²⁺ influx slows single synaptic vesicle endocytosis.

Author information

1
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.

Abstract

Ca²⁺-dependent synaptic vesicle recycling is critical for maintenance of neurotransmission. However, uncoupling the roles of Ca²⁺ in synaptic vesicle fusion and retrieval has been difficult, as studies probing the role of Ca²⁺ in endocytosis relied on measurements of bulk synaptic vesicle retrieval. Here, to dissect the role of Ca²⁺ in these processes, we used a low signal-to-noise pHluorin-tagged vesicular probe to monitor single synaptic vesicle recycling in rat hippocampal neurons. We show that Ca²⁺ increases synaptic vesicle fusion probability in the classical sense, but surprisingly decreases the rate of synaptic vesicle retrieval. This negative regulation of synaptic vesicle retrieval is blocked by the Ca²⁺ chelator, EGTA, as well as FK506, a specific inhibitor of Ca²⁺-calmodulin-dependent phosphatase calcineurin. The slow time course of aggregate synaptic vesicle retrieval detected during repetitive activity could be explained by a progressive decrease in the rate of synaptic vesicle retrieval during the stimulation train. These results indicate that Ca²⁺ entry during single action potentials slows the pace of subsequent synaptic vesicle recycling.

PMID:
22072683
PMCID:
PMC3235053
DOI:
10.1523/JNEUROSCI.3358-11.2011
[Indexed for MEDLINE]
Free PMC Article

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