title: Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.
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.
authors.affiliation: 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.
authors.forename: Igor
authors.initials: I
authors.lastname: Delvendahl
authors.affiliation: Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany;
authors.forename: Lukasz
authors.initials: L
authors.lastname: Jablonski
authors.affiliation: Carl-Ludwig-Institute for Physiology, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany;
authors.forename: Carolin
authors.initials: C
authors.lastname: Baade
authors.affiliation: Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, NJ 07102;
authors.forename: Victor
authors.initials: V
authors.lastname: Matveev
authors.affiliation: Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany igor.delvendahl@medizin.uni-leipzig.de eneher@gwdg.de hallermann@medizin.uni-leipzig.de.
authors.forename: Erwin
authors.initials: E
authors.lastname: Neher
authors.affiliation: 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.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hallermann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D002118:Calcium
keywords: active zone; calcium buffers; calcium signaling; neurotransmitter release; presynaptic