Abstract
Repetitive nerve firings cause short-term depression (STD) of release at many synapses. Its underlying mechanism is largely attributed to depletion of a readily releasable vesicle pool (RRP) and a decreased probability of releasing a readily releasable vesicle during an action potential. Which of these two mechanisms is dominant and the mechanism that decreases the release probability remain debated. Here, we report that a decreased release probability is caused by a calcium-induced inhibition of presynaptic calcium channels, particularly P/Q-type channels at the calyx of Held in rat brainstem. This mechanism was the dominant cause of STD in a wide range of stimulation conditions, such as during 2 to 20 action potential-equivalent stimuli (AP-e) at 0.2-30 Hz and after 2 to 20 AP-e at 0.2-100 Hz. Only during > or = 100 Hz AP-e was depletion the dominant mechanism.
Publication types
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Comparative Study
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Research Support, N.I.H., Intramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Action Potentials / radiation effects
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Animals
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Animals, Newborn
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Barium / pharmacology
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Brain Stem / cytology
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CREB-Binding Protein
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Calcium / metabolism*
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Calcium Channels / drug effects
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Calcium Channels / metabolism*
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Calcium Channels / radiation effects
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Chelating Agents / pharmacology
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Dose-Response Relationship, Radiation
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Egtazic Acid / analogs & derivatives*
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Egtazic Acid / pharmacology
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Electric Capacitance
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Electric Stimulation / methods
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Enzyme Inhibitors / pharmacology
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Imidazoles / pharmacology
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In Vitro Techniques
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Models, Biological
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neural Inhibition / radiation effects
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Nuclear Proteins / pharmacology
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Patch-Clamp Techniques / methods
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Peptides / pharmacology
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism*
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Rats
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Rats, Wistar
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Synapses / metabolism*
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Time Factors
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Trans-Activators / pharmacology
Substances
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Calcium Channels
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Chelating Agents
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Enzyme Inhibitors
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Imidazoles
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Nuclear Proteins
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Peptides
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Trans-Activators
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MLCK peptide
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Barium
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calmidazolium
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Egtazic Acid
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CREB-Binding Protein
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Crebbp protein, rat
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Calcium