Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling

Igor Delvendahl, Lukasz Jablonski, Carolin Baade, Victor Matveev, Erwin Neher, Stefan Hallermann

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)E3075-E3084
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Jun 9 2015

All Science Journal Classification (ASJC) codes

  • General


  • Active zone
  • Calcium buffers
  • Calcium signaling
  • Neurotransmitter release
  • Presynaptic


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