The number of vesicles released and channel cooperativity as a function of variation in model parameters. A, The average number of vesicles released for the standard model (4 open channels; single-channel ICa = 0.1 pA; mobile buffer concentration, 0.1 mm; KD = 2 μm) compared with that when some of the geometrical and non-geometrical model parameters are varied. The geometrical variations that we explored were to constrain all of the open channels to the central row (far from vesicles) or lateral row (close to vesicles) or to restrict all of the Ca2+ binding sites to the side of the vesicle opposite the channels, as opposed to the side closest to the channels. The non-geometrical variations tested were to replace the mobile buffer with the fixed buffer (with the same amount and affinity), to decrease or increase the single-channel current duration (0.3 or 3 vs 1 ms), to use a Gaussian single-channel current waveform with the same total influx, to decrease or increase the single-channel current duration (0.3 or 3 vs 1 ms), and to increase the Ca2+ binding site dissociation constant to KD = 30 μm (from 10 μm) by either increasing the off-rate or decreasing the on-rate as indicated. B, The channel cooperativity resulting from the parameter variations indicated in A as compared with the standard model.