title: Parvalbumin is a mobile presynaptic Ca2+ buffer in the calyx of Held that accelerates the decay of Ca2+ and short-term facilitation.
abstract: Presynaptic Ca2+ signaling plays a crucial role in short-term plasticity of synaptic transmission. Here, we studied the role of mobile endogenous presynaptic Ca2+ buffer(s) in modulating paired-pulse facilitation at a large excitatory nerve terminal in the auditory brainstem, the calyx of Held. To do so, we assessed the effect of presynaptic whole-cell recording, which should lead to the diffusional loss of endogenous mobile Ca2+ buffers, on paired-pulse facilitation and on intracellular Ca2+ concentration ([Ca2+]i) transients evoked by action potentials. In unperturbed calyces briefly preloaded with the Ca2+ indicator fura-6F, the [Ca2+]i transient decayed surprisingly fast (tau(fast), approximately 30 ms). Presynaptic whole-cell recordings made without additional Ca2+ buffers slowed the decay kinetics of [Ca2+]i and paired-pulse facilitation (twofold to threefold), but the amplitude of the [Ca2+]i transient was changed only marginally. The fast [Ca2+]i decay was restored by adding the slow Ca2+ buffer EGTA (50-100 microM) or parvalbumin (100 microM), a Ca2+-binding protein with slow Ca2+-binding kinetics, to the presynaptic pipette solution. In contrast, the fast Ca2+ buffer fura-2 strongly reduced the amplitude of the [Ca2+]i transient and slowed its decay, suggesting that the mobile endogenous buffer in calyces of Held has slow, rather than fast, binding kinetics. In parvalbumin knock-out mice, the decay of [Ca2+]i and facilitation was slowed approximately twofold compared with wild-type mice, similar to what is observed during whole-cell recordings in rat calyces of Held. Thus, in young calyces of Held, a mobile Ca2+ buffer with slow binding kinetics, primarily represented by parvalbumin, accelerates the decay of spatially averaged [Ca2+]i and paired-pulse facilitation.
authors.affiliation: Laboratory of Synaptic Mechanisms, Brain-Mind Institute, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.forename: Felix
authors.initials: F
authors.lastname: Felmy
authors.forename: Beat
authors.initials: B
authors.lastname: Schwaller
authors.forename: Ralf
authors.initials: R
authors.lastname: Schneggenburger
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D010320:Parvalbumins / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D010320:Parvalbumins; D017661:Receptors, Presynaptic; D002118:Calcium