N-type Ca super(2+) channels carry the largest current: implications for nanodomains and transmitter release

• Published in: Nature neuroscience Vol. 13; no. 11; pp. 1348 - 1350
• Main Authors: Weber, Alexander M, Wong, Fiona K, Tufford, Adele R, Schlichter, Lyanne C, Matveev, Victor, Stanley, Elise F
• Format: Journal Article
• Language: English
• Published: 01-11-2010
• ISSN: 1097-6256
• DOI: 10.1038/nn.2657

Presynaptic terminals favor intermediate-conductance Ca sub(V)2.2 (N type) over high-conductance Ca sub(V)1 (L type) channels for single-channel, Ca super(2+) nanodomain-triggered synaptic vesicle fusion. However, the standard Ca sub(V)1>Ca sub(V)2&#x00 3E; Ca sub(V)3 conductance hierarchy is based on recordings using nonphysiological divalent ion concentrations. We found that, with physiological Ca super(2+) gradients, the hierarchy was Ca sub(V)2.2>Ca sub(V)1&#x 003E; Ca sub(V)3. Mathematical modeling predicts that the Ca sub(V)2.2 Ca super(2+) nanodomain, which is 25% more extensive than that generated by Ca sub(V)1, can activate a calcium-fusion sensor located on the proximal face of the synaptic vesicle.