Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 1;64(12):36.
doi: 10.1167/iovs.64.12.36.

A Simplified Model of Activation and Deactivation of Human Rod Phototransduction-An Electroretinographic Study

James D Akula  1   2 , Annie M Lancos  1 , Bilal K AlWattar  1   2 , Hanna De Bruyn  1 , Ronald M Hansen  1   2 , Anne B Fulton  1   2
Affiliations

A Simplified Model of Activation and Deactivation of Human Rod Phototransduction-An Electroretinographic Study

James D Akula et al. Invest Ophthalmol Vis Sci. .

Abstract

Purpose: To test the hypothesis that a simple model having properties consistent with activation and deactivation in the rod approximates the whole time course of the photoresponse.

Methods: Routinely, an exponential of the form f = α·(1 - exp(-(τ·(t - teff)s-1))), with amplitude α, rate constant τ (often scaled by intensity), irreducible delay teff, and time exponent s-1, is fit to the early period of the flash electroretinogram. Notably, s (an integer) represents the three integrating stages in the rod amplification cascade (rhodopsin isomerization, transducin activation, and cGMP hydrolysis). The time course of the photoresponse to a 0.17 cd·s·m-2 conditioning flash (CF) was determined in 21 healthy eyes by presenting the CF plus a bright probe flash (PF) in tandem, separated by interstimulus intervals (ISIs) of 0.01 to 1.4 seconds, and calculating the proportion of the PF a-wave suppressed by the CF at each ISI. To test if similar kinetics describe deactivation, difference of exponential (DoE) functions with common α and teff parameters, respective rate constants for the initiation (I) and quenching (Q) phases of the response, and specified values of s (sI, sQ), were compared to the photoresponse time course.

Results: As hypothesized, the optimal values of sI and sQ were 3 and 2, respectively. Mean ± SD α was 0.80 ± 0.066, I was 7700 ± 2400 m2·cd-1·s-3, and Q was 1.4 ± 0.47 s-1. Overall, r2 was 0.93.

Conclusions: A method, including a DoE model with just three free parameters (α, I, Q), that robustly captures the magnitude and time-constants of the complete rod response, was produced. Only two steps integrate to quench the rod photoresponse.

PubMed Disclaimer

Conflict of interest statement

Disclosure: J.D. Akula, None; A.M. Lancos, None; B.K. AlWattar, None; H. De Bruyn, None; R.M. Hansen, None; A.B. Fulton, None

Figures

Figure 1.
Figure 1.
Representative example of the “double-flash” protocol for estimating suppression of the dark current, SFt. Top: In the dark-adapted eye, the responses to an a-wave–saturating (20 cd·s·m–2) PF (maroon trace) and a 0.17 cd·s·m–2 CF (green trace) were each recorded alone. Then the CF and PF were presented in tandem, separated by 10 ISIs; in these double-flash cases, the responses were aligned 10 ms prior to presentation of the PF. The amplitudes of the responses to the PF (orange lines) were measured 10 ms after PF presentation, taking the response to the CF, recorded alone, as the baseline for the measurement of the double-flash responses (black traces) at each ISI. Bottom: This shows the proportion of the rod response suppressed by the PF (maroon point) and by the CF at each ISI (black points). The orange lines help to visualize the waning and waxing of the dark current “underneath” the intact ERG (green trace).
Figure 2.
Figure 2.
Modeling the response to the PF. The first 20 ms of each volunteer’s response to a bright (20 cd·s·m–2) stimulus are shown (gray traces), as is their mean (black trace). Fits of the first 10 ms (circles) of these data to Equation 1 with sI values of 2 (stippled cyan line), 3 (red line), and 4 (stippled purple line) are shown. For the best-fitting model (sI = 3), the value of teff was ∼3.2 ms (arrow).
Figure 3.
Figure 3.
Plots of the suppression of the dark current, SFt, derived using the double-flash ERG protocol detailed in Figure 1, in every volunteer (black lines and circles) and fits of the hypothesized DoE model (red lines) with three integrating steps in the initiation and two integrating steps in the quenching of the rod photoresponse. The overall r is 0.97 (Table).
Figure 4.
Figure 4.
Replot of the individual SFt values from Figure 3 (gray) and superimposed mean SFts (black) on a linear (top) and—to provide a better view of the rapid initiation phase of the photoresponse—a logarithmic (bottom) time scale. The fits of these data to Equation 2, with sI = 3 and sQ values of 2 (red line), 3 (stippled cyan line), and 4 (stippled purple line), are shown.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Curcio CA, Sloan KR, Kalina RE, Hendrickson AE.. Human photoreceptor topography. J Comp Neurol. 1990; 292: 497–523. - PubMed
    1. Granit R. Sensory Mechanisms of the Retina, With an Appendix on Electroretinography. New York, NY: Hafner; 1963.
    1. Pugh EN Jr, Falsini B, Lyubarsky AL. The origins of the major rod- and cone-driven components of the rodent electroretinogram and the effect of age and light-rearing history on the magnitude of these components. In: Williams, TP, Thistle AB, eds. Photostasis and Related Phenomena . New York, NY: Plenum Press; 1998: 93–128.
    1. Pugh EN Jr, Lamb TD. Amplification and kinetics of the activation steps in phototransduction. Biochim Biophys Acta. 1993; 1141: 111–149. - PubMed
    1. Hood DC, Birch DG.. Light adaptation of human rod receptors: the leading edge of the human a-wave and models of rod receptor activity. Vis Res. 1993; 33: 1605–1618. - PubMed

Publication types

-