N-type Ca2+ channels carry the largest current: implications for nanodomains and transmitter release

• DOI: 10.1038/nn.2657
• Publication Date: 2010-10-17T18:25:00Z
• Authors: Alexander M Weber; Fiona K Wong; Adele R Tufford; Lyanne C Schlichter; Victor Matveev; Elise F Stanley
• Keywords: Neuroscientist

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.