title: Ca2+ buffer saturation underlies paired pulse facilitation in calbindin-D28k-containing terminals.
abstract: Ca2+ buffer saturation was proposed as a mechanism of paired pulse facilitation (PPF). However, whether it operates under native conditions remained unclear. Here we show that saturation of the endogenous fast Ca2+ buffer calbindin-D28k (CB) plays a major role in PPF at CB-containing synapses. Paired recordings from synaptically connected interneurons and pyramidal neurons in the mouse neocortex revealed that dialysis increased the amplitude of the first response and decreased PPF. Loading the presynaptic terminals with BAPTA or CB rescued the effect of the CB washout. We extended the study to the CB-positive facilitating excitatory mossy fiber-CA3 pyramidal cell synapse. The effects of different extracellular Ca2+ concentrations and of EGTA indicated that PPF in CB-containing terminals depended on Ca2+ influx rather than on the initial release probability. Experiments in CB knockout mice confirmed that buffer saturation is a novel basic presynaptic mechanism for activity-dependent control of synaptic gain.
authors.affiliation: Department of Clinical Neurobiology, University Hospital for Neurology, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Blatow
authors.forename: Antonio
authors.initials: A
authors.lastname: Caputi
authors.forename: Nail
authors.initials: N
authors.lastname: Burnashev
authors.forename: Hannah
authors.initials: H
authors.lastname: Monyer
authors.forename: Andrei
authors.initials: A
authors.lastname: Rozov
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002021:Buffers; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003956:Dialysis; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism; D019579:Neocortex / Q000166:cytology; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D002021:Buffers; C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D002614:Chelating Agents; D064030:S100 Calcium Binding Protein G; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium