The cGMP-phosphodiesterase and its contribution to sensitivity regulation in retinal rods

Koutalos, Yiannis; Nakatani, Keigo; Yau, King Wai

doi:10.1085/jgp.106.5.891

Cited by 95 publications

(113 citation statements)

References 65 publications

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“…Steady-state circulating current- Koutalos et al (1995) presented an analysis of light adaptation and its effects on circulating current in rods. They measured circulating current from salamander rods under control conditions (Ringer's) and under Ca 2+ clamp in which the effect of Ca 2+ feedback onto several loci in the cascade was presumably effectively shut down.…”

Section: The Model Captures Steady-state Light-adapted Rod Response Fmentioning

confidence: 99%

“…One of the important contributions of the Koutalos et al (1995) paper was that they also attempted to quantify the relative contribution of three Ca 2+ -feedback pathways to steady-state light adaptation of circulating current. Using parameter estimates from the literature and from their own measurements, they modeled Ca 2+ -feedback modulation of (1) cyclase synthesis via GCAPs and guanylate cyclase (e.g.…”

Section: The Model Captures Steady-state Light-adapted Rod Response Fmentioning

confidence: 99%

“…Specifically, if the model could account for single-photon response features, but failed to reproduce realistic responses in the high light regime, including light adaptation (LA), the model would have to be modified in a fundamental way. Toward this end, we adjusted the model in an attempt to account for six important classes of rod data: (1) SPR waveforms and statistics (as in Hamer et al, 2003), including SPR reproducibility; (2) a full dark-adapted flash-response series (obtained in the present study), from dim-flash to saturating, bright flash levels, obtained from a toad rod; (3) steady-state LA responses, including LA circulating current (as in Koutalos et al, 1995) and LA flash sensitivity measured in rods from four species; (4) step responses from newt rods (Forti et al, 1989) over a large dynamic range; (5) dynamic LA responses, such as the step-flash paradigm of Fain et al (1989), and the two-flash paradigm of Murnick and Lamb (1996); and (6) the salient response features from four knockout (KO) rod preparations.…”

Section: Introductionmentioning

confidence: 99%

“…A dark-adapted flash series, and stimulus paradigms from the literature eliciting various degrees of light adaptation (LA), were simulated using a full differential equation version of the model that included the addition of Ca 2+ -feedback onto rhodopsin kinase via recoverin. With this model, using a single set of parameters, we attempted to account for (1) SPR waveforms and statistics (as in Hamer et al, 2003); (2) a full darkadapted flash-response series, from dim flash to saturating, bright flash levels, from a toad rod; (3) steady-state LA responses, including LA circulating current (as in Koutalos et al, 1995) and LA flash sensitivity measured in rods from four species; (4) step responses from newt rods (Forti et al, 1989) over a large dynamic range; (5) dynamic LA responses, such as the step-flash paradigm of Fain et al (1989), and the two-flash paradigm of Murnick and Lamb (1996); and (6) the salient response features from four knockout rod preparations. The model was able to meet this stringent test, accounting for almost all the salient qualitative, and many quantitative features, of the responses across this broad array of stimulus conditions, including SPR reproducibility.…”

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confidence: 99%

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Toward a unified model of vertebrate rod phototransduction

et al. 2005

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Recently, we introduced a phototransduction model that was able to account for the reproducibility of vertebrate rod single-photon responses (SPRs) (Hamer et al., 2003). The model was able to reproduce SPR statistics by means of stochastic activation and inactivation of rhodopsin (R*), transducin (G α ), and phosphodiesterase (PDE). The features needed to capture the SPR statistics were (1) multiple steps of R* inactivation by means of multiple phosphorylations (followed by arrestin capping) and (2) phosphorylation dependence of the affinity between R* and the three molecules competing to bind with R* (G α , arrestin, and rhodopsin kinase). The model was also able to account for several other rod response features in the dim-flash regime, including SPRs obtained from rods in which various elements of the cascade have been genetically disabled or disrupted. However, the model was not tested under high light-level conditions. We sought to evaluate the extent to which the multiple phosphorylation model could simultaneously account for single-photon response behavior, as well as responses to high light levels causing complete response saturation and/or significant light adaptation (LA). To date no single model, with one set of parameters, has been able to do this. Dim-flash responses and statistics were simulated using a hybrid stochastic/ deterministic model and Monte-Carlo methods as in Hamer et al. (2003). A dark-adapted flash series, and stimulus paradigms from the literature eliciting various degrees of light adaptation (LA), were simulated using a full differential equation version of the model that included the addition of Ca 2+ -feedback onto rhodopsin kinase via recoverin. With this model, using a single set of parameters, we attempted to account for (1) SPR waveforms and statistics (as in Hamer et al., 2003); (2) a full darkadapted flash-response series, from dim flash to saturating, bright flash levels, from a toad rod; (3) steady-state LA responses, including LA circulating current (as in Koutalos et al., 1995) and LA flash sensitivity measured in rods from four species; (4) step responses from newt rods (Forti et al., 1989) over a large dynamic range; (5) dynamic LA responses, such as the step-flash paradigm of Fain et al. (1989), and the two-flash paradigm of Murnick and Lamb (1996); and (6) the salient response features from four knockout rod preparations. The model was able to meet this stringent test, accounting for almost all the salient qualitative, and many quantitative features, of the responses across this broad array of stimulus conditions, including SPR reproducibility. The model promises to be useful in testing hypotheses regarding both normal and abnormal photoreceptor function, and is a good starting point for development of a full-range model of cone phototransduction. Informative limitations of the model are also discussed.

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Section: The Model Captures Steady-state Light-adapted Rod Response Fmentioning

confidence: 99%

Section: The Model Captures Steady-state Light-adapted Rod Response Fmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Toward a unified model of vertebrate rod phototransduction

et al. 2005

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“…Model calculations based on the Ca 2þ dependence of the various components of the transduction cascade indicate that the contribution of channel modulation to light adaptation is likely to be rather small. (73) But if the reopening of the channels in bright light doesn't contribute to light adaptation, what does it do? I suggest that the channels reopen to prevent the Ca 2þ from going too low for too long, to keep the cell from dying.…”

Section: Why Does Continuous Activation Kill?mentioning

confidence: 99%

Why photoreceptors die (and why they don't)

Fain

2006

BioEssays

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Light can kill the photoreceptors of the eye, not only very bright direct sunlight, but more moderate illumination if the light is present continuously. Recent experiments show that rod apoptosis can be triggered by strong and constant activation of transduction, and that death can be prevented if transduction is inhibited even though the eye is illuminated. Vitamin A deficiency and genetically inherited diseases, such as some forms of retinitis pigmentosa and Leber congenital amaurosis, appear to kill like this: transduction is activated at a high rate and continuously, and this causes the rods to die. Why does transduction kill? Our best guess is that continuous activation produces a prolonged lowering of the Ca2+ concentration, which is also thought to kill neurons in tissue culture and during the development of the nervous system. To prevent death in constant light, rods have evolved protective mechanisms including modulation of channels and ion transport to keep the Ca2+ from going too low. Prolonged light exposure also causes migration of transduction proteins from one part of the cell to another and a reversible shortening of the rod outer segments, the part of the cell that contains the pigment rhodopsin. All of these mechanisms are at work in the normal eye to reduce transduction and prevent the Ca2+ concentration from dropping too low for too long a time. That most of us retain our vision our entire lives is a testament to their effectiveness. BioEssays 28: 344–354, 2006. © 2006 Wiley Periodicals, Inc.

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