title: Spatial Distribution of Calcium Entry Evoked by Single Action Potentials within the Presynaptic Active Zone.
abstract: The nature of presynaptic calcium (Ca(2+)) signals that initiate neurotransmitter release makes these signals difficult to study, in part because of the small size of specialized active zones within most nerve terminals. Using the frog motor nerve terminal, which contains especially large active zones, we show that increases in intracellular Ca(2+) concentration within 1 msec of action potential invasion are attributable to Ca(2+) entry through N-type Ca(2+) channels and are not uniformly distributed throughout active zone regions. Furthermore, changes in the location and magnitude of Ca(2+) signals recorded before and after experimental manipulations (omega-conotoxin GVIA, diaminopyridine, and lowered extracellular Ca(2+)) support the hypothesis that there is a remarkably low probability of a single Ca(2+) channel opening within an active zone after an action potential. The trial-to-trial variability observed in the spatial distribution of presynaptic Ca(2+) entry also supports this conclusion, which differs from the conclusions of previous work in other synapses.
authors.affiliation: Center for Light Microscope Imaging and Biotechnology, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Wachman
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poage
authors.forename: Joel R
authors.initials: JR
authors.lastname: Stiles
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Farkas
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Meriney
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence / Q000379:methods; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011894:Rana pipiens / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D005456:Fluorescent Dyes; D026902:Potassium Channel Blockers; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D020866:omega-Conotoxin GVIA; D002118:Calcium