July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Rod photoreceptor transition intensity between dominant time constants indicates a high rate of transducin activation
Author Affiliations & Notes
  • Trevor D Lamb
    Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia
  • Timothy W Kraft
    Department of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Trevor Lamb, None; Timothy Kraft, None
  • Footnotes
    Support  NEI Grant R01EY023603
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1007. doi:
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      Trevor D Lamb, Timothy W Kraft; Rod photoreceptor transition intensity between dominant time constants indicates a high rate of transducin activation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1007.

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

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Abstract

Purpose : To model the responses of mammalian rod photoreceptors to bright flashes of light, and thereby to examine the predicted time in saturation (Tsat) as a function of flash intensity (Φ photoisomerisations). Thence to determine the rate (νRG) of transducin activation per photoisomerisation, that is required to account for the measured transition intensity (Φtrans) for the change from lower to higher dominant time constant of recovery.

Methods : We modelled mammalian rod photoreceptor responses to bright flashes using two approaches: (i) stochastic simulation of the 2D diffusional reactions on the disc membrane; and (ii) a much faster analytical description, applicable at late times, once the distribution of molecules on the disc membrane is spatially uniform. We analysed a new model of dimeric PDE6 activation [Open Biol. 8, 180075], as well as the conventional model of independent activation of PDE6 subunits. We took account of the rate constant kG* for decay of free G* (activated transducin) in the absence of binding to PDE6, mediated by RGS9. We solved for specified numbers of isomerisations per disc surface, and then modelled the downstream cytoplasmic reactions in response to a Poisson distribution of isomerisations on individual discs.

Results : We evaluated the time-course of PDE6 activation, E**(t) in the dimeric model, and the time-course of the electrical response, and then measured the time in saturation, and plotted Tsat against Φ logarithmically in Fig. 1. In order to achieve correspondence with experimental results in the literature, we found it essential to adopt a high rate of transducin activation, of νRG > 1000 G*/s/R*. For Fig. 1 we used νRG = 1600 G*/s/R*, a mean R* lifetime of 68 ms, kE** = 5 s-1 and kG* = 1.25 s-1, together with a total number of PDE6 holomers in the outer segment of 140,000; this gave the transition intensity (intercept of straight-line fits) as Φtrans ≈ 4000 R*.

Conclusions : We conclude, firstly, that our model provides a good description of mammalian rod bright-flash responses and, secondly, that it shows that the rate of transducin activation is likely to be considerably in excess of 1000 G*/s per R*.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Fig. 1. Predicted saturation time Tsat (red) versus flash intensity Φ, logarithmically, from 200 to 60,000 R*/rod. Symbols: from Fig. 4B of Burns & Pugh (2010) Physiology 25, 72-84. Dotted lines: time constants of 250 ms and 660 ms.

Fig. 1. Predicted saturation time Tsat (red) versus flash intensity Φ, logarithmically, from 200 to 60,000 R*/rod. Symbols: from Fig. 4B of Burns & Pugh (2010) Physiology 25, 72-84. Dotted lines: time constants of 250 ms and 660 ms.

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