Quantitative analysis of synaptic release at the photoreceptor synapse.
Exocytosis from the rod photoreceptor is stimulated by submicromolar Ca(2+) and exhibits an unusually shallow dependence on presynaptic Ca(2+). To provide a quantitative description of the photoreceptor Ca(2+) sensor for exocytosis, we tested a family of conventional and allosteric computational models describing the final Ca(2+)-binding steps leading to exocytosis. Simulations were fit to two measures of release, evoked by flash-photolysis of caged Ca(2+): exocytotic capacitance changes from individual rods and postsynaptic currents of second-order neurons. The best simulations supported the occupancy of only two Ca(2+) binding sites on the rod Ca(2+) sensor rather than the typical four or five. For most models, the on-rates for Ca(2+) binding and maximal fusion rate were comparable to those of other neurons. However, the off-rates for Ca(2+) unbinding were unexpectedly slow. In addition to contributing to the high-affinity of the photoreceptor Ca(2+) sensor, slow Ca(2+) unbinding may support the fusion of vesicles located at a distance from Ca(2+) channels. In addition, partial sensor occupancy due to slow unbinding may contribute to the linearization of the first synapse in vision.
Duncan
Gabriel
G
Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Rabl
Katalin
K
Gemp
Ian
I
Heidelberger
Ruth
R
Thoreson
Wallace B
WB
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D025802:Electric Capacitance; D004558:Electric Stimulation; D004594:Electrophysiology / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009433:Neural Inhibition; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D010786:Photoreceptor Cells / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D051248:Retinal Horizontal Cells / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014562:Caudata; D014785:Vision, Ocular / Q000502:physiology*