scholarly journals Onset of Feedback Reactions Underlying Vertebrate Rod Photoreceptor Light Adaptation

1998 ◽  
Vol 111 (1) ◽  
pp. 39-51 ◽  
Author(s):  
Peter D. Calvert ◽  
Theresa W. Ho ◽  
Yvette M. LeFebvre ◽  
Vadim Y. Arshavsky
Keyword(s):  
Guanylate Cyclase ◽  
Light Adaptation ◽  
Continuous Illumination ◽  
Enzymatic Reactions ◽  
Rod Photoreceptor ◽  
Cgmp Phosphodiesterase ◽  
Rhodopsin Kinase ◽  
Slow Dissociation ◽  
Kinetics Of ◽  
Flash Response

Light adaptation in vertebrate photoreceptors is thought to be mediated through a number of biochemical feedback reactions that reduce the sensitivity of the photoreceptor and accelerate the kinetics of the photoresponse. Ca2+ plays a major role in this process by regulating several components of the phototransduction cascade. Guanylate cyclase and rhodopsin kinase are suggested to be the major sites regulated by Ca2+. Recently, it was proposed that cGMP may be another messenger of light adaptation since it is able to regulate the rate of transducin GTPase and thus the lifetime of activated cGMP phosphodiesterase. Here we report measurements of the rates at which the changes in Ca2+ and cGMP are followed by the changes in the rates of corresponding enzymatic reactions in frog rod outer segments. Our data indicate that there is a temporal hierarchy among reactions that underlie light adaptation. Guanylate cyclase activity and rhodopsin phosphorylation respond to changes in Ca2+ very rapidly, on a subsecond time scale. This enables them to accelerate the falling phase of the flash response and to modulate flash sensitivity during continuous illumination. To the contrary, the acceleration of transducin GTPase, even after significant reduction in cGMP, occurs over several tens of seconds. It is substantially delayed by the slow dissociation of cGMP from the noncatalytic sites for cGMP binding located on cGMP phosphodiesterase. Therefore, cGMP-dependent regulation of transducin GTPase is likely to occur only during prolonged bright illumination.

scholarly journals A quantitative account of mammalian rod phototransduction with PDE6 dimeric activation: responses to bright flashes

Open Biology ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 190241
Author(s):  
Trevor D. Lamb ◽  
Timothy W. Kraft
Keyword(s):  
Quantitative Model ◽  
Rod Photoreceptor ◽  
Flash Intensity ◽  
Rod Photoreceptors ◽  
Membrane Surfaces ◽  
Bright Flash ◽  
The Relationship ◽  
Kinetics Of ◽  
Quantitative Account ◽  
Flash Response

We develop an improved quantitative model of mammalian rod phototransduction, and we apply it to the prediction of responses to bright flashes of light. We take account of the recently characterized dimeric nature of PDE6 activation, where the configuration of primary importance has two transducin molecules bound. We simulate the stochastic nature of the activation and shut-off reactions to generate the predicted kinetics of the active molecular species on the disc membrane surfaces, and then we integrate the differential equations for the downstream cytoplasmic reactions to obtain the predicted electrical responses. The simulated responses recover the qualitative form of bright-flash response families recorded from mammalian rod photoreceptors. Furthermore, they provide an accurate description of the relationship between the time spent in saturation and flash intensity, predicting the transition between first and second ‘dominant time constants’ to occur at an intensity around 5000 isomerizations per flash, when the rate of transducin activation is taken to be 1250 transducins s −1 per activated rhodopsin. This rate is consistent with estimates from light-scattering experiments, but is around fourfold higher than has typically been assumed in other studies. We conclude that our model and parameters provide a compelling description of rod photoreceptor bright-flash responses.

scholarly journals Calcium dependence of the activation and inactivation kinetics of the light-activated phosphodiesterase of retinal rods.

1989 ◽  
Vol 93 (6) ◽  
pp. 1091-1108 ◽  
Author(s):  
A E Barkdoll ◽  
E N Pugh ◽  
A Sitaramayya
Keyword(s):  
Light Adaptation ◽  
Peak Velocity ◽  
Formal Analysis ◽  
Light Sensitivity ◽  
Inactivation Kinetics ◽  
Time To Peak ◽  
Rhodopsin Kinase ◽  
Reconstituted System ◽  
Kinetics Of

The Ca2+ dependence of the kinetics and light sensitivity of light-activated phosphodiesterase was studied with a pH assay in toad and bovine rod disk membranes (RDM), and in a reconstituted system containing GTP-binding protein, phosphodiesterase and rhodopsin kinase. Three statistics, peak hydrolytic velocity, turnoff time, and time to peak velocity, were measured. ATP decreased phosphodiesterase light sensitivity nearly 10-fold and accelerated the dim-flash kinetics of cGMP hydrolysis when compared to those with GTP alone. CA2+ reversed all of the effects of ATP, Ca2+ increased peak velocity, turnoff time, and time to peak velocity, to the values obtained with GTP alone. The Ca2+ dependence of peak velocity and turnoff time can be characterized as hyperbolic saturation functions with a K0.5 for Ca2+ of 1.0-1.5 mM in toad RDM. In bovine RDM the Ca2+ dependence of peak velocity and turnoff time has a K0.5 of 0.1 mM Ca2+. The Ca2+ dependence in the reconstituted system is similar to that in bovine RDM for peak velocity (K0.5 = 0.1 mM Ca2+) but differs for turnoff time (K0.5 = 2.5 mM Ca2+). We tested the hypothesis that a soluble modulator, normally required to confer submicromolar Ca2+ sensitivity, was too dilute in our assay by comparing data obtained at one RDM concentration with those obtained at 10-fold higher RDM, and therefore a constituent protein, concentration. We observe no difference and present a formal analysis of these data that excludes the hypothesis that the soluble modulator binds its target protein with Kd less than 5 microM. The lack of submicromolar Ca2+ dependence of any of the steps in the cGMP cascade that underlie cGMP phosphodiesterase activation and inactivation in vitro argues against Ca2+ regulation of these steps having a significant role in the light adaptation of the intact rod.

scholarly journals Approximation theorems of a solution of amperometric enzymatic reactions based on Green’s fixed point normal-S iteration

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
Khanitin Muangchoo-in ◽  
Kanokwan Sitthithakerngkiet ◽  
Parinya Sa-Ngiamsunthorn ◽  
Poom Kumam
Keyword(s):  
Fixed Point ◽  
Boundary Value Problems ◽  
Iterative Methods ◽  
Dynamical Problem ◽  
Enzymatic Reactions ◽  
Nonlinear Dynamical ◽  
Numerical Examples ◽  
Approximation Theorems ◽  
Kinetics Of ◽  
Nonlinear Dynamical Problem

AbstractIn this paper, the authors present a strategy based on fixed point iterative methods to solve a nonlinear dynamical problem in a form of Green’s function with boundary value problems. First, the authors construct the sequence named Green’s normal-S iteration to show that the sequence converges strongly to a fixed point, this sequence was constructed based on the kinetics of the amperometric enzyme problem. Finally, the authors show numerical examples to analyze the solution of that problem.

Assignment of the ?-subunit of rod photoreceptor cGMP phosphodiesterase gene PDEB (homolog of the mouse gene) to human chromosome 4p16

Genomics ◽  
1992 ◽  
Vol 12 (3) ◽  
pp. 601-603 ◽  
Author(s):  
J BATEMAN ◽  
I KLISAK ◽  
T KOJIS ◽  
T MOHANDAS ◽  
R SPARKES ◽  
...  
Keyword(s):  
Human Chromosome ◽  
Mouse Gene ◽  
Rod Photoreceptor ◽  
Cgmp Phosphodiesterase ◽  
Chromosome 4P16

scholarly journals Psychomotor stimulant effects of α-pyrrolidinovalerophenone (αPVP) enantiomers correlate with drug binding kinetics at the dopamine transporter

2021 ◽  
Author(s):  
Marco Niello ◽  
Spyridon Sideromenos ◽  
Ralph Gradisch ◽  
Ronan O'Shea ◽  
Jakob Schwazer ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
In Silico ◽  
Drug Binding ◽  
Binding Kinetics ◽  
Irreversible Binding ◽  
Fast Kinetics ◽  
Slow Dissociation ◽  
Kinetics Of

Abstract α-Pyrrolidinovalerophenone (αPVP) is a psychostimulant and drug of abuse associated with severe intoxications in humans. αPVP exerts long-lasting psychostimulant effects, when compared to the classical dopamine transporter (DAT) inhibitor cocaine. Here, we compared the two enantiomeric forms of αPVP, the R- and the S-αPVP, with cocaine using a combination of in silico, in vitro and in vivo approaches. We found that αPVP enantiomers substantially differ from cocaine in their binding kinetics. The two enantiomers differ from each other in their association rates. However, they show similar slow dissociation rates leading to pseudo-irreversible binding kinetics at DAT. The pseudo-irreversible binding kinetics of αPVP is responsible for the observed non-competitive pharmacology and it correlates with persistent psychostimulant effects in mice. Thus, the slow binding kinetics of αPVP enantiomers profoundly differ from the fast kinetics of cocaine both in vitro and in vivo, suggesting drug-binding kinetics as a potential driver of psychostimulant effects in vivo.

The human β-subunit of rod photoreceptor cGMP phosphodiesterase: Complete retinal cDNA sequence and evidence for expression in brain

Genomics ◽  
1992 ◽  
Vol 13 (3) ◽  
pp. 698-704 ◽  
Author(s):  
Colin Collins ◽  
Gordon Hutchinson ◽  
David Kowbel ◽  
Olaf Riess ◽  
Bernhard Weber ◽  
...  
Keyword(s):  
Cdna Sequence ◽  
Rod Photoreceptor ◽  
Β Subunit ◽  
Cgmp Phosphodiesterase

Slow light and dark adaptation of horizontal cells in the Xenopus retina: A role for endogenous dopamine

1990 ◽  
Vol 5 (04) ◽  
pp. 405-413 ◽  
Author(s):  
Paul Witkovsky ◽  
Xiao-Ping Shi
Keyword(s):  
Light Adaptation ◽  
Slow Light ◽  
Horizontal Cell ◽  
Cell Communication ◽  
Dark Field ◽  
Subsequent Treatment ◽  
Complete Suppression ◽  
Retinal Neuron ◽  
Endogenous Dopamine ◽  
Kinetics Of

AbstractA role for endogenous dopamine in the control of rod and contributions to a second-order retinal neuron, the horizontal cell (HC) was studied in theXenopusretina. Relative rod and cone contributions were estimated from HC responses to scotopically balanced 491- and 650-nm flashes. In eyecups prepared in light then placed in darkness, cone input to the HC slowed and diminished on a time scale of hours. The decline in cone input was balanced by a slow growth of rod input to the HC. Administration of D-amphetamine, a dopamine releasing agent, restored the light-adapted waveform.The kinetics of slow light adaptation were examined by recording HC responses from eyecups that had been dark-adapted previously for 11–14 h. When test flashes fell on a dark field, cone input to the HC grew for 2–4 h, reached a plateau, and later declined. If, however, flashes were superimposed on a weak background field, cone input to the HC continued to increase monotonically at about 10%/h. This increase was abolished by superfusion with a nonspecific dopamine receptor blocker, cis-flupenthixol (50 μM), resulting in the complete suppression of cone-to-horizontal cell synaptic transfer and the enhancement of rod-to-horizontal cell communication. Subcutaneous injection of reserpine, a drug that depletes dopamine stores (2 mg/kg on 1–4 successive days), or intraocular injection of the dopamine neurotoxin, 6-hydroxydopamine (10–30 μg) slowed and reduced the amplitude of cone input to the HC, even in completely light-adapted eyes. Subsequent treatment with D-amphetamine (5–50 μM) or dopamine (10 μM) partially restored the normal response.Our experimental findings are consistent with the following hypothesis. Weak light is sufficient to stimulate dopamine release; dopamine augments cone-to-horizontal cell synaptic transfer and reduces rod-to-horizontal cell communication. The rapid kinetics of the fully light-adapted response depend on the presence of dopamine. Thus, dopamine appears to be an intraretinal signal for slow light adaptation.

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