Modeling and simulation of phototransduction cascade in vertebrate rod photoreceptors

Pan, Guofeng; Tan, Jinglu; Guo, Ya

doi:10.1186/s12886-019-1048-7

Cited by 3 publications

(17 citation statements)

References 25 publications

(37 reference statements)

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“…Transducin's alpha subunit binds to phosphodiesterase and makes it activated. This can be represented as (Pan et al 2019)…”

Section: Activation Of Phosphodiesterase By Activated G*mentioning

confidence: 99%

“…E * catalyses the hydrolysis of cGMP(denoted as cG ) and produces GMP . According to Michaelis-Menten kinetics, this process can be represented as (Pan et al 2019) where C 2 is the intermediate complex formed by the binding of E * and cG , k 2 , k 3 and k 4 are reaction rate constants.…”

Section: Change Of Cyclic Gmp Concentrationmentioning

confidence: 99%

“…The GTP bound to G * in the complex of E * is hydrolyzed to GDP, which results in separation of the complex, production of PDE and G − GDP G r . This process can be represented as (Pan et al 2019)…”

Section: Inactivation Of E*mentioning

confidence: 99%

“…Now due to closing of the channels, the inward flow of calcium ions is reduced. If x 6 denotes the concentration of calcium ions inside the photoreceptor, then the drop in calcium ion concentration is mathematically written as (Pan et al 2019)…”

Section: Channel Activitymentioning

confidence: 99%

“…In order to explain the effects of iron-induced oxidative stress, the different molecules and ions involved in phototransduction are quantified and we follow the terminology given in Pan et al (2019).…”

Section: Introductionmentioning

confidence: 99%

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The $$a$$-Wave of the Electroretinogram and Iron-Induced Oxidative Stress: A Model

et al. 2021

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In photoreceptors of a dark adapted eye, the inward flux of sodium and calcium ions in the outer segment is balanced by the outward flux of potassium ions. But in the presence of light the creation of cyclic guanosine monophosphate in the outer segment decreases. Due to low concentration of cG (cyclic GMP) the channels in the outer segment open relatively less and thus the influx of calcium ion decreases, leading finally to hyperpolarization of the photoreceptors. We have analyzed theoretically the effect of oxidizing iron ions on the photoreceptors. In order to explain the effects of iron-induced oxidative stress, the different molecules and ions involved in phototransduction are quantified leading to a differential equation for calculating the electroretinogram a-wave voltage. The theoretical results are compared with published experimental data. In the presence of light, the iron ions could push outward the similarly charged calcium ions resulting in a small increase in the amount of inward calcium flux. Again, the presence of iron ions generates Reactive Oxygen Species, and ROS could attract the calcium ions which also increases the calcium flux. This will result in a reduction in the amplitude and slope of the a-wave voltage in the electroretinogram. These results are parametrized in terms of calcium ion concentrations. As the amplitude of the a-wave shows how much electrical signal is produced, its reduction indicates reduction in the visual signal. Thus, the increase in iron ions could explain the reduction in the electrical signal due to iron-induced oxidative stress.

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“…Transducin's alpha subunit binds to phosphodiesterase and makes it activated. This can be represented as (Pan et al 2019)…”

Section: Activation Of Phosphodiesterase By Activated G*mentioning

confidence: 99%

Section: Change Of Cyclic Gmp Concentrationmentioning

confidence: 99%

Section: Inactivation Of E*mentioning

confidence: 99%

Section: Channel Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The $$a$$-Wave of the Electroretinogram and Iron-Induced Oxidative Stress: A Model

et al. 2021

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Homeostasis at different backgrounds: The roles of overlayed feedback structures in vertebrate photoadaptation

2023

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We have studied the resetting behavior of eight basic integral controller motifs with respect to different but constant backgrounds. We found that the controllers split symmetrically into two classes: one class, based on derepression of the compensatory flux, leads to more rapid resetting kinetics as backgrounds increase. The other class, which directly activates the compensatory flux, shows a slowing down in the resetting at increased backgrounds. We found a striking analogy between the resetting kinetics of vertebrate photoreceptors and controllers based on derepression, i.e. vertebrate rod or cone cells show decreased sensitivities and accelerated response kinetics as background illuminations increase. The central molecular model of vertebrate photoadaptation consists of an overlay of three negative feedback loops with cytosolic calcium (Ca i 2 +), cyclic guanosine monophosphate (cGMP) and cyclic nucleotide-gated (CNG) channels as components. While in one of the feedback loops the extrusion of Ca i 2 + by potassium-dependent sodium-calcium exchangers (NCKX) can lead to integral control with cGMP as the controlled variable, the expected robust perfect adaptation of cGMP is lost, because of the two other feedback loops. They avoid that Ca i 2 + levels become too high and toxic. Looking at psychophysical laws, we found that in all of the above mentioned basic controllers Weber’s law is followed when a “just noticeable difference” (threshold) of 1% of the controlled variable’s set-point was considered. Applying comparable threshold pulses or steps to the photoadaptation model we find, in agreement with experimental results, that Weber’s law is followed for relatively high backgrounds, while Stephens’ power law gives a better description when backgrounds are low. Limitations of our photoadaption model, in particular with respect to potassium/sodium homeostasis, are discussed. Finally, we discuss possible implication of background perturbations in biological controllers when compensatory fluxes are based on activation.

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Murburn model of vision supports multi-layered photoreception and signal relay networks in human eye

Manoj,

Jacob

2023

Preprint

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From Maheswaranathan et al.’s work published in your journal Neuron (July 2023), we note the report of computational modelling of image/signal processing within the retina, advocating a three-layered network that included interneurons and ganglion cells. As seen from globally recognized personas, popular textbooks, timely reviews, and state of the science research communications on molecular/macroscopic visual cycle, the new pitch extends beyond the conventional view of photo-transduction (photoreception), which is conventionally depicted to occur at the rod cell outer segments (RCOS), within the rod/cone cell layer in the distal part of retina, adjacent to the retinal pigment epithelium (or RPE). Over the last two and a half decades, we have pioneered a novel paradigm called murburn concept, which posits that diffusible reactive (oxygen) species (DRS/DROS) are obligatorily involved in affecting/effecting routine molecular/macroscopic cascades in cellular physiology. Within the ambit of this pursuit, we had originally disseminated a cover-page credited piece in Biomedical Reviews (30th annual volume of the Bulgarian Society of Cell Biology published in 2020) quoting architectural, photo-biochemical and evolutionary rationales for the murburn model of vision. The current work by Maheswaranathan et al. gains physiological validation by our pre-dated ‘murburn’ pursuits.

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Modeling and simulation of phototransduction cascade in vertebrate rod photoreceptors

Cited by 3 publications

References 25 publications

The $$a$$-Wave of the Electroretinogram and Iron-Induced Oxidative Stress: A Model

The $$a$$-Wave of the Electroretinogram and Iron-Induced Oxidative Stress: A Model

Homeostasis at different backgrounds: The roles of overlayed feedback structures in vertebrate photoadaptation

Murburn model of vision supports multi-layered photoreception and signal relay networks in human eye

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