1. National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Building 35, Room 2B-1012, Bethesda, Maryland 20892, USA

Correspondence to: Ling-Gang Wu¹ Correspondence and requests for materials should be addressed to L.G.W. (Email: wul@ninds.nih.gov).

Fusion of a vesicle with the cell membrane opens a pore that releases transmitter to the extracellular space^{1, 2, 3}. The pore can either dilate fully so that the vesicle collapses completely, or close rapidly to generate 'kiss-and-run' fusion^{1, 2, 4, 5, 6, 7}. The size of the pore determines the release rate². At synapses, the size of the fusion pore is unclear, 'kiss-and-run' remains controversial^{8, 9, 10, 11, 12, 13, 14, 15}, and the ability of 'kiss-and-run' fusion to generate rapid synaptic currents^{16, 17} is questionable¹⁸. Here, by recording fusion pore kinetics during single vesicle fusion, we found both full collapse and 'kiss-and-run' fusion at calyx-type synapses. For full collapse, the initial fusion pore conductance (G_p) was usually >375 pS and increased rapidly at 299 pS ms^–1. 'Kiss-and-run' fusion was seen as a brief capacitance flicker (<2 s) with G_p >288 pS for most flickers, but within 15–288 pS for the remaining flickers. Large G_p (>288 pS) might discharge transmitter rapidly and thereby cause rapid synaptic currents, whereas small G_p might generate slow and small synaptic currents. These results show that 'kiss-and-run' fusion occurs at synapses and that it can generate rapid postsynaptic currents, and suggest that various fusion pore sizes help to control the kinetics and amplitude of synaptic currents.

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