Faculty Opinions recommendation of Bright flash response recovery of mammalian rods in vivo is rate limited by RGS9.

2017 ◽  
Author(s):  
Gordon Fain
Keyword(s):  
Response Recovery ◽  
Bright Flash ◽  
Flash Response

scholarly journals Origin and control of the dominant time constant of salamander cone photoreceptors

2012 ◽  
Vol 140 (2) ◽  
pp. 219-233 ◽  
Author(s):  
Jingjing Zang ◽  
Hugh R. Matthews
Keyword(s):  
Time Constant ◽  
External Solution ◽  
Light Response ◽  
Response Recovery ◽  
Bright Flash ◽  
Active Intermediates ◽  
And Control ◽  
Flash Response ◽  
Phototransduction Cascade ◽  
External Ph

Recovery of the light response in vertebrate photoreceptors requires the shutoff of both active intermediates in the phototransduction cascade: the visual pigment and the transducin–phosphodiesterase complex. Whichever intermediate quenches more slowly will dominate photoresponse recovery. In suction pipette recordings from isolated salamander ultraviolet- and blue-sensitive cones, response recovery was delayed, and the dominant time constant slowed when internal [Ca2+] was prevented from changing after a bright flash by exposure to 0Ca2+/0Na+ solution. Taken together with a similar prior observation in salamander red-sensitive cones, these observations indicate that the dominance of response recovery by a Ca2+-sensitive process is a general feature of amphibian cone phototransduction. Moreover, changes in the external pH also influenced the dominant time constant of red-sensitive cones even when changes in internal [Ca2+] were prevented. Because the cone photopigment is, uniquely, exposed to the external solution, this may represent a direct effect of protons on the equilibrium between its inactive Meta I and active Meta II forms, consistent with the notion that the process dominating recovery of the bright flash response represents quenching of the active Meta II form of the cone photopigment.

scholarly journals Prolongation of Actions of Ca2+ Early in Phototransduction by 9-Demethylretinal

2001 ◽  
Vol 118 (4) ◽  
pp. 377-390 ◽  
Author(s):  
Hugh R. Matthews ◽  
M.C. Cornwall ◽  
R.K. Crouch
Keyword(s):  
Outer Segment ◽  
Time Course ◽  
Calcium Concentration ◽  
Surface Membrane ◽  
Background Intensity ◽  
Cytoplasmic Calcium ◽  
Response Recovery ◽  
Bright Flash ◽  
Flash Response

During adaptation Ca2+ acts on a step early in phototransduction, which is normally available for only a brief period after excitation. To investigate the identity of this step, we studied the effect of the light-induced decline in intracellular Ca2+ concentration on the response to a bright flash in normal rods, and in rods bleached and regenerated with 11-cis 9-demethylretinal, which forms a photopigment with a prolonged photoactivated lifetime. Changes in cytoplasmic Ca2+ were opposed by rapid superfusion of the outer segment with a 0Na+/0Ca2+ solution designed to minimize Ca2+ fluxes across the surface membrane. After regeneration of a bleached rod with 9-demethlyretinal, the response in Ringer's to a 440-nm bright flash was prolonged in comparison with the unbleached control, and the response remained in saturation for 10–15s. If the dynamic fall in Ca2+i induced by the flash was delayed by stepping the outer segment to 0Na+/0Ca2+ solution just before the flash and returning it to Ringer's shortly before recovery, then the response saturation was prolonged further, increasing linearly by 0.41 ± 0.01 of the time spent in this solution. In contrast, even long exposures to 0Na+/0Ca2+ solution of rods containing native photopigment evoked only a modest response prolongation on the return to Ringer's. Furthermore, if the rod was preexposed to steady subsaturating light, thereby reducing the cytoplasmic calcium concentration, then the prolongation of the bright flash response evoked by 0Na+/0Ca2+ solution was reduced in a graded manner with increasing background intensity. These results indicate that altering the chromophore of rhodopsin prolongs the time course of the Ca2+-dependent step early in the transduction cascade so that it dominates response recovery, and suggest that it is associated with photopigment quenching by phosphorylation.

scholarly journals Novel Form of Adaptation in Mouse Retinal Rods Speeds Recovery of Phototransduction

2003 ◽  
Vol 122 (6) ◽  
pp. 703-712 ◽  
Author(s):  
Claudia M. Krispel ◽  
Ching-Kang Chen ◽  
Melvin I. Simon ◽  
Marie E. Burns
Keyword(s):  
Dark Current ◽  
Bright Light ◽  
Ambient Light ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Electrophysiological Recordings ◽  
Bright Flash ◽  
Retinal Rods ◽  
Rate Limiting ◽  
Flash Response

Photoreceptors of the retina adapt to ambient light in a manner that allows them to detect changes in illumination over an enormous range of intensities. We have discovered a novel form of adaptation in mouse rods that persists long after the light has been extinguished and the rod's circulating dark current has returned. Electrophysiological recordings from individual rods showed that the time that a bright flash response remained in saturation was significantly shorter if the rod had been previously exposed to bright light. This persistent adaptation did not decrease the rate of rise of the response and therefore cannot be attributed to a decrease in the gain of transduction. Instead, this adaptation was accompanied by a marked speeding of the recovery of the response, suggesting that the step that rate-limits recovery had been accelerated. Experiments on knockout rods in which the identity of the rate-limiting step is known suggest that this adaptive acceleration results from a speeding of G protein/effector deactivation.

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 Physiological and Microfluorometric Studies of Reduction and Clearance of Retinal in Bleached Rod Photoreceptors

2004 ◽  
Vol 124 (4) ◽  
pp. 429-443 ◽  
Author(s):  
Efthymia Tsina ◽  
Chunhe Chen ◽  
Yiannis Koutalos ◽  
Petri Ala-Laurila ◽  
Marco Tsacopoulos ◽  
...  
Keyword(s):  
Dark Adaptation ◽  
Bright Light ◽  
Proximal Region ◽  
Rod Photoreceptors ◽  
Outer Segments ◽  
Interphotoreceptor Retinoid Binding Protein ◽  
Response Recovery ◽  
Electrophysiological Measurements ◽  
Rate Of Recovery ◽  
Flash Response

The visual cycle comprises a sequence of reactions that regenerate the visual pigment in photoreceptors during dark adaptation, starting with the reduction of all-trans retinal to all-trans retinol and its clearance from photoreceptors. We have followed the reduction of retinal and clearance of retinol within bleached outer segments of red rods isolated from salamander retina by measuring its intrinsic fluorescence. Following exposure to a bright light (bleach), increasing fluorescence intensity was observed to propagate along the outer segments in a direction from the proximal region adjacent to the inner segment toward the distal tip. Peak retinol fluorescence was achieved after ∼30 min, after which it declined very slowly. Clearance of retinol fluorescence is considerably accelerated by the presence of the exogenous lipophilic substances IRBP (interphotoreceptor retinoid binding protein) and serum albumin. We have used simultaneous fluorometric and electrophysiological measurements to compare the rate of reduction of all-trans retinal to all-trans retinol to the rate of recovery of flash response amplitude in these cells in the presence and absence of IRBP. We find that flash response recovery in rods is modestly accelerated in the presence of extracellular IRBP. These results suggest such substances may participate in the clearance of retinoids from rod photoreceptors, and that this clearance, at least in rods, may facilitate dark adaptation by accelerating the clearance of photoproducts of bleaching.

scholarly journals Actions of Ca2+ on an Early Stage in Phototransduction Revealed by the Dynamic Fall in Ca2+ Concentration during the Bright Flash Response

1997 ◽  
Vol 109 (2) ◽  
pp. 141-146 ◽  
Author(s):  
H.R. Matthews
Keyword(s):  
Time Constant ◽  
Outer Segment ◽  
Calcium Concentration ◽  
Early Stage ◽  
Ringer Solution ◽  
Cytoplasmic Calcium ◽  
Rod Outer Segment ◽  
Bright Flash ◽  
A Site ◽  
Flash Response

To study the actions of Ca2+ on “early” stages of the transduction cascade, changes in cytoplasmic calcium concentration (Ca2+i) were opposed by manipulating Ca2+ fluxes across the rod outer segment membrane immediately following a bright flash. If the outer segment was exposed to 0 Ca2+/0 Na+ solution for a brief period immediately after the flash, then the period of response saturation was prolonged in comparison with that in Ringer solution. But if the exposure to 0 Ca2+/0 Na+ solution instead came before or was delayed until 1 s after the flash then it had little effect. The degree of response prolongation increased with the duration of the exposure to 0 Ca2+/0 Na+ solution, revealing a time constant of 0.49 ± 0.03 s. By the time the response begins to recover from saturation, Ca2+i seems likely to have fallen to a similar level in each case. Therefore the prolongation of the response when Ca2+i was prevented from changing immediately after the flash seems likely to reflect the abolition of actions of the usual dynamic fall in Ca2+i on an early stage in the transduction cascade at a site which is available for only a brief period after the flash. One possibility is that the observed time constant corresponds to the phosphorylation of photoisomerized rhodopsin.

scholarly journals Bright flash response recovery of mammalian rods in vivo is rate limited by RGS9

2017 ◽  
Vol 149 (4) ◽  
pp. 443-454 ◽  
Author(s):  
Gabriel Peinado Allina ◽  
Christopher Fortenbach ◽  
Franklin Naarendorp ◽  
Owen P. Gross ◽  
Edward N. Pugh ◽  
...  
Keyword(s):  
G Protein ◽  
Wheel Running ◽  
Ex Vivo ◽  
Scotopic Vision ◽  
Bright Flash ◽  
Wide Range ◽  
Genetic Perturbations ◽  
Rate Limiting ◽  
Kinetics Of

The temporal resolution of scotopic vision is thought to be constrained by the signaling kinetics of retinal rods, which use a highly amplified G-protein cascade to transduce absorbed photons into changes in membrane potential. Much is known about the biochemical mechanisms that determine the kinetics of rod responses ex vivo, but the rate-limiting mechanisms in vivo are unknown. Using paired flash electroretinograms with improved signal-to-noise, we have recorded the amplitude and kinetics of rod responses to a wide range of flash strengths from living mice. Bright rod responses in vivo recovered nearly twice as fast as all previous recordings, although the kinetic consequences of genetic perturbations previously studied ex vivo were qualitatively similar. In vivo, the dominant time constant of recovery from bright flashes was dramatically reduced by overexpression of the RGS9 complex, revealing G-protein deactivation to be rate limiting for recovery. However, unlike previous ex vivo recordings, dim flash responses in vivo were relatively unaffected by RGS9 overexpression, suggesting that other mechanisms, such as calcium feedback dynamics that are strongly regulated by the restricted subretinal microenvironment, act to determine rod dim flash kinetics. To assess the consequences for scotopic vision, we used a nocturnal wheel-running assay to measure the ability of wild-type and RGS9-overexpressing mice to detect dim flickering stimuli and found no improvement when rod recovery was speeded by RGS9 overexpression. These results are important for understanding retinal circuitry, in particular as modeled in the large literature that addresses the relationship between the kinetics and sensitivity of retinal responses and visual perception.

scholarly journals Functional modulation of phosphodiesterase-6 by calcium in mouse rod photoreceptors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Teemu Turunen ◽  
Ari Koskelainen
Keyword(s):  
Photoreceptor Cells ◽  
Light Sensitivity ◽  
Common View ◽  
Thermally Activated ◽  
Response Recovery ◽  
Vertebrate Photoreceptor ◽  
Intracellular Ca ◽  
Sensor Proteins ◽  
Cgmp Synthesis ◽  
Flash Response

AbstractPhosphodiesterase-6 (PDE6) is a key protein in the G-protein cascade converting photon information to bioelectrical signals in vertebrate photoreceptor cells. Here, we demonstrate that PDE6 is regulated by calcium, contrary to the common view that PDE1 is the unique PDE class whose activity is modulated by intracellular Ca2+. To broaden the operating range of photoreceptors, mammalian rod photoresponse recovery is accelerated mainly by two calcium sensor proteins: recoverin, modulating the lifetime of activated rhodopsin, and guanylate cyclase-activating proteins (GCAPs), regulating the cGMP synthesis. We found that decreasing rod intracellular Ca2+concentration accelerates the flash response recovery and increases the basal PDE6 activity (βdark) maximally by ~ 30% when recording local electroretinography across the rod outer segment layer from GCAPs−/−recoverin−/−mice. Our modeling shows that a similar elevation in βdarkcan fully explain the observed acceleration of flash response recovery in low Ca2+. Additionally, a reduction of the free Ca2+in GCAPs−/−recoverin−/−rods shifted the inhibition constants of competitive PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) against the thermally activated and light-activated forms of PDE6 to opposite directions, indicating a complex interaction between IBMX, PDE6, and calcium. The discovered regulation of PDE6 is a previously unknown mechanism in the Ca2+-mediated modulation of rod light sensitivity.

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