Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling

Document Type

Article

Publication Date

6-9-2015

Abstract

Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca2+ signals, which are confined in their spatiotemporal extent by endogenous Ca2+ buffers. However, it remains elusive how rapid and reliable Ca2+ signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca2+ imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca2+-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 Ca2+ from the active zone during repetitive firing. Measuring Ca2+ signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca2+ buffering enables fast active zone Ca2+ signaling, suggesting that the strength of endogenous Ca2+ buffering limits the rate of synchronous synaptic transmission.

Identifier

84931291943 (Scopus)

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

External Full Text Location

https://doi.org/10.1073/pnas.1508419112

e-ISSN

10916490

ISSN

00278424

PubMed ID

26015575

First Page

E3075

Last Page

E3084

Issue

23

Volume

112

Grant

DMS-0817703

Fund Ref

National Science Foundation

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