Quantitative analysis of synaptic release at the photoreceptor synapse

Exocytosis from the rod photoreceptor Is stimulated by submicromolar Ca²⁺ and exhibits an unusually shallow dependence on presynaptic Ca²⁺. To provide a quantitative description of the photoreceptor Ca²⁺ sensor for exocytosis, we tested a family of conventional and allosteric computational models describing the final Ca²⁺-binding steps leading to exocytosis. Simulations were fit to two measures of release, evoked by flash-photolysis of caged Ca²⁺: exocytotlc capacitance changes from individual rods and postsynaptic currents of second-order neurons. The best simulations supported the occupancy of only two Ca²⁺ binding sites on the rod Ca²⁺ sensor rather than the typical four or five. For most models, the on-rates for Ca²⁺ binding and maximal fusion rate were comparable to those of other neurons. However, the off-rates for Ca²⁺ unbinding were unexpectedly slow. In addition to contributing to the high-affinity of the photoreceptor Ca²⁺ sensor, slow Ca ²⁺ unbinding may support the fusion of vesicles located at a distance from Ca²⁺ channels. In addition, partial sensor occupancy due to slow unbinding may contribute to the linearization of the first synapse In vision.