title: Control of synaptic strength and timing by the release-site Ca2+ signal.
abstract: Transmitter release is triggered by highly localized, transient increases in the presynaptic Ca(2+) concentration ([Ca(2+)]). Rapidly decaying [Ca(2+)] elevations were generated using Ca(2+) uncaging techniques, and [Ca(2+)] was measured with a low-affinity Ca(2+) indicator in a giant presynaptic terminal, the calyx of Held, in rat brain slices. The rise time and amplitude of evoked excitatory postsynaptic currents (EPSCs) depended on the half-width of the fluorescence transient, which was predicted by a five-binding site model of a Ca(2+) sensor having relatively high affinity (K(d) approximately 13 microM). Very fast [Ca(2+)] transients (half-width <0.5 ms) evoked EPSCs similar to those elicited by a single action potential (AP) in the same synapse. Triggering release with dual [Ca(2+)] transients of variable amplitudes demonstrated the supralinear transfer function of the sensor. The sensitivity of release to the time course of the [Ca(2+)] transient may contribute to mechanisms by which the presynaptic AP waveform controls synaptic strength.
authors.affiliation: Abteilung Zellphysiologie, Max-Planck-Institut für medizinische Forschung, Jahnstrasse 29, D-69120 Heidelberg, Germany. johann@mcb.harvard.edu
authors.forename: Johann H
authors.initials: JH
authors.lastname: Bollmann
authors.forename: Bert
authors.initials: B
authors.lastname: Sakmann
mesh_terms: D000085:Acetates / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001581:Benzothiadiazines / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005029:Ethylenediamines / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D007834:Lasers; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010782:Photolysis / Q000528:radiation effects; D011237:Predictive Value of Tests; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D000085:Acetates; D001581:Benzothiadiazines; D002614:Chelating Agents; D005029:Ethylenediamines; C057014:DM-nitrophen; D018698:Glutamic Acid; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002122:Calcium Chloride; C004639:cyclothiazide; D002118:Calcium