Abstract

Exocytosis from the rod photoreceptor is stimulated by submicromolar calcium and exhibits an unusually shallow dependence on presynaptic calcium. This weak cooperativity may contribute to the linear relationship between calcium influx and release at photoreceptor synapses and contrasts with release at other ribbon and conventional synapses, which exhibit a fourth or fifth-order calcium dependence. To provide a quantitative description of the photoreceptor calcium sensor for exocytosis, we tested a family of conventional and allosteric computational models describing the final calcium-binding steps leading to exocytosis. Simulations were fit to two measures of release, evoked by flash-photolysis of caged calcium: exocytotic capacitance changes from individual rods and post-synaptic currents of second-order neurons. The best simulations supported the occupancy of only two calcium binding sites on the rod sensor rather than the typical four or five. For most models, the on-rates for calcium binding and maximal fusion rate were comparable to those of other neurons. However, the off-rates for calcium unbinding were unexpectedly slow. In addition to contributing to the high-affinity of the photoreceptor calcium sensor, slow calcium unbinding may support the fusion of vesicles located at a distance from calcium channels, perhaps located higher up the synaptic ribbon or away from the ribbon. In addition, partial sensor occupancy due to slow unbinding may further contribute to the linearization at this first synapse in vision.

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