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The Limit of Photoreceptor Sensitivity: Molecular Mechanisms of Dark Noise in Retinal Cones
Detection threshold in cone photoreceptors requires the simultaneous absorption of several photons because single photon photocurrent is small in amplitude and does not exceed intrinsic fluctuations in the outer segment dark current (dark noise). To understand the mechanisms that limit light sensiti...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234084/ https://www.ncbi.nlm.nih.gov/pubmed/15928405 http://dx.doi.org/10.1085/jgp.200509277 |
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author | Holcman, David Korenbrot, Juan I. |
author_facet | Holcman, David Korenbrot, Juan I. |
author_sort | Holcman, David |
collection | PubMed |
description | Detection threshold in cone photoreceptors requires the simultaneous absorption of several photons because single photon photocurrent is small in amplitude and does not exceed intrinsic fluctuations in the outer segment dark current (dark noise). To understand the mechanisms that limit light sensitivity, we characterized the molecular origin of dark noise in intact, isolated bass single cones. Dark noise is caused by continuous fluctuations in the cytoplasmic concentrations of both cGMP and Ca(2+) that arise from the activity in darkness of both guanylate cyclase (GC), the enzyme that synthesizes cGMP, and phosphodiesterase (PDE), the enzyme that hydrolyzes it. In cones loaded with high concentration Ca(2+) buffering agents, we demonstrate that variation in cGMP levels arise from fluctuations in the mean PDE enzymatic activity. The rates of PDE activation and inactivation determine the quantitative characteristics of the dark noise power density spectrum. We developed a mathematical model based on the dynamics of PDE activity that accurately predicts this power spectrum. Analysis of the experimental data with the theoretical model allows us to determine the rates of PDE activation and deactivation in the intact photoreceptor. In fish cones, the mean lifetime of active PDE at room temperature is ∼55 ms. In nonmammalian rods, in contrast, active PDE lifetime is ∼555 ms. This remarkable difference helps explain why cones are noisier than rods and why cone photocurrents are smaller in peak amplitude and faster in time course than those in rods. Both these features make cones less light sensitive than rods. |
format | Text |
id | pubmed-2234084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22340842008-03-21 The Limit of Photoreceptor Sensitivity: Molecular Mechanisms of Dark Noise in Retinal Cones Holcman, David Korenbrot, Juan I. J Gen Physiol Article Detection threshold in cone photoreceptors requires the simultaneous absorption of several photons because single photon photocurrent is small in amplitude and does not exceed intrinsic fluctuations in the outer segment dark current (dark noise). To understand the mechanisms that limit light sensitivity, we characterized the molecular origin of dark noise in intact, isolated bass single cones. Dark noise is caused by continuous fluctuations in the cytoplasmic concentrations of both cGMP and Ca(2+) that arise from the activity in darkness of both guanylate cyclase (GC), the enzyme that synthesizes cGMP, and phosphodiesterase (PDE), the enzyme that hydrolyzes it. In cones loaded with high concentration Ca(2+) buffering agents, we demonstrate that variation in cGMP levels arise from fluctuations in the mean PDE enzymatic activity. The rates of PDE activation and inactivation determine the quantitative characteristics of the dark noise power density spectrum. We developed a mathematical model based on the dynamics of PDE activity that accurately predicts this power spectrum. Analysis of the experimental data with the theoretical model allows us to determine the rates of PDE activation and deactivation in the intact photoreceptor. In fish cones, the mean lifetime of active PDE at room temperature is ∼55 ms. In nonmammalian rods, in contrast, active PDE lifetime is ∼555 ms. This remarkable difference helps explain why cones are noisier than rods and why cone photocurrents are smaller in peak amplitude and faster in time course than those in rods. Both these features make cones less light sensitive than rods. The Rockefeller University Press 2005-06 /pmc/articles/PMC2234084/ /pubmed/15928405 http://dx.doi.org/10.1085/jgp.200509277 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Holcman, David Korenbrot, Juan I. The Limit of Photoreceptor Sensitivity: Molecular Mechanisms of Dark Noise in Retinal Cones |
title | The Limit of Photoreceptor Sensitivity: Molecular Mechanisms of Dark Noise in Retinal Cones |
title_full | The Limit of Photoreceptor Sensitivity: Molecular Mechanisms of Dark Noise in Retinal Cones |
title_fullStr | The Limit of Photoreceptor Sensitivity: Molecular Mechanisms of Dark Noise in Retinal Cones |
title_full_unstemmed | The Limit of Photoreceptor Sensitivity: Molecular Mechanisms of Dark Noise in Retinal Cones |
title_short | The Limit of Photoreceptor Sensitivity: Molecular Mechanisms of Dark Noise in Retinal Cones |
title_sort | limit of photoreceptor sensitivity: molecular mechanisms of dark noise in retinal cones |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234084/ https://www.ncbi.nlm.nih.gov/pubmed/15928405 http://dx.doi.org/10.1085/jgp.200509277 |
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