N-type Ca2+ channels carry the largest current: implications for nanodomains and transmitter release.
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.
Laboratory of Synaptic Transmission, Toronto Western Research Institute, Toronto, Ontario, Canada.
Alexander M
AM
Weber
Fiona K
FK
Wong
Adele R
AR
Tufford
Lyanne C
LC
Schlichter
Victor
V
Matveev
Elise F
EF
Stanley
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000145:classification / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008433:Mathematics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D011237:Predictive Value of Tests; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013572:Synaptic Vesicles / Q000378:metabolism
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018377:Neurotransmitter Agents; D002118:Calcium