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Journal Article

Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling


Neher,  E.
Emeritus Group of Membrane Biophysics, MPI for Biophysical Chemistry, Max Planck Society;

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Delvendahl, I., Jablonski, L., Baade, C., Matveev, V., Neher, E., & Hallermann, S. (2015). Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling. Proceedings of the National Academy of Sciences of the United States of America, 112(23), E3075-E3084. doi:10.1073/pnas.1508419112.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0027-BBA4-E
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 (similar to 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.