May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Avoidance of Saturation in Human Cones Is Explained by Very Rapid Inactivation Reactions and Pigment Bleaching
Author Affiliations & Notes
  • T.D. Lamb
    Divn of Neuroscience, JCSMR and ARC Centre of Excellence in Vision Science, Australian National University, Canberra, Australia
  • E.N. Pugh, Jr.
    Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships  T.D. Lamb, None; E.N. Pugh, None.
  • Footnotes
    Support  ARC FF0344672 and CE0561903; NIH EY–02660; RPB Foundation
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 3714. doi:
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      T.D. Lamb, E.N. Pugh, Jr.; Avoidance of Saturation in Human Cones Is Explained by Very Rapid Inactivation Reactions and Pigment Bleaching . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3714.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To account for the ability of human cones to avoid saturation of their circulating current in very bright illumination.

Methods: : Response properties of human cones were predicted on the basis of a previous theoretical model of adaptation in rod transduction [1], using recent estimates for the speed of shut–off reactions [2–4].

Results: : Because of pigment bleaching, the steady rate of photoisomerization cannot exceed the maximal rate of pigment regeneration, ∼400,000 molecules s–1 in human cones [4]. Does cone saturation occur at this rate of isomerization? Recent reports indicate that the time constants τR and τE for inactivation of R* (activated pigment) and E* (activated transducin–PDE complex) in human/primate cones are both very short, even in dim light. Values for τR and τE have been estimated as ∼3.4 ms and ∼8–18 ms [2, 3], though it is not possible to determine which value represents τR and which τE. With extremely bright illumination, time constants of 5 and 13 ms have been shown to provide an adequate fit to the a–wave "off response" [4], consistent with little effect of light intensity on these time constants. In contrast, in mammalian rods the time constants τR and τE are estimated to be around 70 and 200 ms [5]. In human rod photoreceptors in vivo, the circulating current is halved at a steady intensity of 70 sc Td (600 isoms s–1), with complete saturation occurring at 1000 sc Td (∼104 isoms s–1). If the activation gain of transduction is the same in human cones as in human rods, then the shorter cone time constants would elevate the intensities required for half– and complete–saturation by some 200–fold, to ∼120,000 and ∼2 × 106 isoms s–1 in cones. Furthermore, in contrast to the cGMP–gated channels of mammalian rods, those of mammalian cones alter their cGMP affinity when Ca2+ drops [6], thereby further increasing the required rate. Hence, the rate of isomerization required to saturate the cone current exceeds the maximal rate at which isomerizations can occur in the steady state.

Conclusions: : Rapid shut–off reactions and pigment bleaching permit human cone photoreceptors to avoid saturation during steady light of arbitrarily high intensity. 1. Nikonov et al (2000). J. Gen. Physiol. 116, 795. 2. van Hateren (2005). J. Vision. 5, 331. 3. Friedburg et al (2004). J. Physiol. 556, 819. 4. Kenkre et al (2005). J. Physiol. 567, 95. 5. Krispel et al (2005). IOVS 46 suppl, 4628. 6. Thomas & Lamb (1999). J. Physiol. 518, 479. 7. Rebrik & Korenbrot (2004). J. Gen. Physiol. 123, 63.

Keywords: photoreceptors: visual performance • electrophysiology: non-clinical 

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