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