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Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):E3075-84. doi: 10.1073/pnas.1508419112. Epub 2015 May 26.

Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.

Author information

1
Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; igor.delvendahl@medizin.uni-leipzig.de eneher@gwdg.de hallermann@medizin.uni-leipzig.de.
2
Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany;
3
Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, NJ 07102;
4
Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany igor.delvendahl@medizin.uni-leipzig.de eneher@gwdg.de hallermann@medizin.uni-leipzig.de.

Abstract

Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca(2+) signals, which are confined in their spatiotemporal extent by endogenous Ca(2+) buffers. However, it remains elusive how rapid and reliable Ca(2+) signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca(2+) imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca(2+)-binding ratio (∼ 15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca(2+) from the active zone during repetitive firing. Measuring Ca(2+) signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca(2+) buffering enables fast active zone Ca(2+) signaling, suggesting that the strength of endogenous Ca(2+) buffering limits the rate of synchronous synaptic transmission.

KEYWORDS:

active zone; calcium buffers; calcium signaling; neurotransmitter release; presynaptic

PMID:
26015575
PMCID:
PMC4466756
DOI:
10.1073/pnas.1508419112
[Indexed for MEDLINE]
Free PMC Article

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