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Owen P. Gross, Edward N. Pugh, Jr., Marie E. Burns; The Contribution Of Calcium Feedback Regulation To Stability And Reproducibility Of Single Photon Responses. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4135.
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Rod photoreceptors generate highly amplified single-photon responses (SPRs) using G-protein signaling that is under strict temporal regulation through tightly determined lifetimes of photoactivated rhodopsin (R*) and the G-protein-PDE complex (G*-E*). Paradoxically, genetic perturbations that dramatically alter these lifetimes have little effect on the amplitudes of SPRs. Our purpose was to investigate how this amplitude stability across genotypes arises, and to test whether the mechanisms governing amplitude stability also contribute to the reproducibility of single photon responses from trial to trial in normal rods.
Mice with faster or slower rates of R* and G*-E* deactivation were crossed into a line lacking calcium feedback regulation of cGMP synthesis (GCAPs-/-), and the photoresponses of rods were measured with suction electrodes. SPRs were extracted from variance-to-mean analysis or by constructing histograms of quantal amplitudes from ensembles of responses to extremely dim flashes.
When calcium feedback mechanisms were abolished, rods with slowed R* and G*-E* deactivation kinetics showed much larger increases in peak amplitudes than when calcium feedback was operating normally. Ensembles of SPRs from rods with and without feedback reveal that the consequences of trial-to-trial fluctuations in R* lifetime in normal rods are likewise dampened by feedback regulation of cGMP synthesis.
Calcium feedback trumps the intricate mechanisms of R* and G*-E* deactivation at the SPR peak, preserving the time-to-peak and attenuating responses arising from longer active lifetimes to a greater extent than those arising from shorter ones. As a result, SPRs are of similar amplitude, a feature critical for reliable transmission through the visual system.
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