Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling*
  • Female
  • In Vitro Techniques
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurotransmitter Agents / metabolism

Substances

  • Neurotransmitter Agents
  • Calcium