Abstract
Presynaptic terminals favor intermediate-conductance Ca(V)2.2 (N type) over high-conductance Ca(V)1 (L type) channels for single-channel, Ca(2+) nanodomain-triggered synaptic vesicle fusion. However, the standard Ca(V)1>Ca(V)2>Ca(V)3 conductance hierarchy is based on recordings using nonphysiological divalent ion concentrations. We found that, with physiological Ca(2+) gradients, the hierarchy was Ca(V)2.2>Ca(V)1>Ca(V)3. Mathematical modeling predicts that the Ca(V)2.2 Ca(2+) nanodomain, which is ∼25% more extensive than that generated by Ca(V)1, can activate a calcium-fusion sensor located on the proximal face of the synaptic vesicle.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Calcium / metabolism
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Calcium / pharmacology
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Calcium Channel Blockers / pharmacology
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Calcium Channels, N-Type / classification
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Calcium Channels, N-Type / physiology*
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Cells, Cultured
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Chick Embryo
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Dose-Response Relationship, Drug
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Ganglia, Spinal / cytology
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology*
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Mathematics
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Membrane Potentials / drug effects
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Membrane Potentials / physiology*
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Models, Biological
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Neural Conduction / drug effects
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Neurons / drug effects
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Neurons / physiology*
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Neurotransmitter Agents / metabolism*
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Patch-Clamp Techniques / methods
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Predictive Value of Tests
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Protein Structure, Tertiary / physiology
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Synaptic Transmission / drug effects
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Synaptic Vesicles / metabolism
Substances
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Calcium Channel Blockers
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Calcium Channels, N-Type
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Neurotransmitter Agents
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Calcium