Calcium feedback to cGMP synthesis strongly attenuates single-photon responses driven by long rhodopsin lifetimes.
Rod photoreceptors generate amplified, reproducible responses to single photons via a G protein signaling cascade. Surprisingly, genetic perturbations that dramatically alter the deactivation of the principal signal amplifier, the GPCR rhodopsin (R∗), do not much alter the amplitude of single-photon responses (SPRs). These same perturbations, when crossed into a line lacking calcium feedback regulation of cGMP synthesis, produced much larger alterations in SPR amplitudes. Analysis of SPRs from rods with and without feedback reveal that the consequences of trial-to-trial fluctuations in R∗ lifetime in normal rods are also dampened by feedback regulation of cGMP synthesis. Thus, calcium feedback trumps the mechanisms of R∗ deactivation in determining the SPR amplitude, attenuating responses arising from longer R∗ lifetimes to a greater extent than those arising from shorter ones. As a result, rod SPRs achieve a more stereotyped amplitude, a characteristic considered important for reliable transmission through the visual system.
Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA.
Owen P
OP
Gross
Edward N
EN
Pugh
Marie E
ME
Burns
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology*; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D051604:Guanylate Cyclase-Activating Proteins / Q000235:genetics; D007930:Leucine / Q000235:genetics; D008390:Markov Chains; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009842:Oligopeptides / Q000235:genetics; D010766:Phosphorylation; D010775:Photic Stimulation; D017785:Photons; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D012243:Rhodopsin / Q000378:metabolism*; D012694:Serine / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
D051604:Guanylate Cyclase-Activating Proteins; D009842:Oligopeptides; D012694:Serine; D012243:Rhodopsin; C045056:gamma-glutamyl-seryl-glycine; D051606:G-Protein-Coupled Receptor Kinase 1; C496762:Grk1 protein, mouse; D007930:Leucine; D006152:Cyclic GMP; D002118:Calcium