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 Photopigment quenching is Ca2+ dependent and controls response duration in salamander L-cone photoreceptors

2010 ◽  
Vol 135 (4) ◽  
pp. 355-366 ◽  
Author(s):  
Hugh R. Matthews ◽  
Alapakkam P. Sampath
Keyword(s):  
Time Constant ◽  
Light Adaptation ◽  
Light Response ◽  
Response Duration ◽  
Photoreceptor Cells ◽  
Quenching Rate ◽  
Vertebrate Photoreceptor ◽  
Cone Response ◽  
Rate Limiting ◽  
Phototransduction Cascade

The time scale of the photoresponse in photoreceptor cells is set by the slowest of the steps that quench the light-induced activity of the phototransduction cascade. In vertebrate photoreceptor cells, this rate-limiting reaction is thought to be either shutoff of catalytic activity in the photopigment or shutoff of the pigment's effector, the transducin-GTP–phosphodiesterase complex. In suction pipette recordings from isolated salamander L-cones, we found that preventing changes in internal [Ca2+] delayed the recovery of the light response and prolonged the dominant time constant for recovery. Evidence that the Ca2+-sensitive step involved the pigment itself was provided by the observation that removal of Cl− from the pigment's anion-binding site accelerated the dominant time constant for response recovery. Collectively, these observations indicate that in L-cones, unlike amphibian rods where the dominant time constant is insensitive to [Ca2+], pigment quenching rate limits recovery and provides an additional mechanism for modulating the cone response during light adaptation.

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 Metabolic constraints on the recovery of sensitivity after visual pigment bleaching in retinal rods

2009 ◽  
Vol 134 (3) ◽  
pp. 165-175 ◽  
Author(s):  
Kiyoharu J. Miyagishima ◽  
M. Carter Cornwall ◽  
Alapakkam P. Sampath
Keyword(s):  
Time Constant ◽  
Visual Pigment ◽  
Outer Segment ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Bright Light ◽  
Primary Source ◽  
Retinal Rods ◽  
Before And After ◽  
Active Intermediates ◽  
Phototransduction Cascade

The shutoff of active intermediates in the phototransduction cascade and the reconstitution of the visual pigment play key roles in the recovery of sensitivity after the exposure to bright light in both rod and cone photoreceptors. Physiological evidence from bleached salamander rods suggests this recovery of sensitivity occurs faster at the outer segment base compared with the tip. Microfluorometric measurements of similarly bleached salamander rods demonstrate that the reduction of all-trans retinal to all-trans retinol also occurs more rapidly at the outer segment base than at the tip. The experiments reported here were designed to test the hypothesis that these two phenomena are linked, e.g., that slowed recovery of sensitivity at the tip of outer segments is rate limited by the reduction of all-trans retinal and results from a shortage of cytosolic nicotinamide adenine dinucleotide phosphate (NADPH), the reducing agent for all-trans retinal reduction. Extracellular measurements of membrane current and sensitivity were made from isolated salamander rods under dark-adapted and bleached conditions while intracellular NADPH concentration was varied by dialysis from a micropipette attached to the inner segment. Sensitivity at the base and tip of the outer segment was assessed before and after bleaching. After exposure to a light that photoactivates 50% of the visual pigment, rods were completely insensitive for nearly 10 minutes, after which the base recovered sensitivity and responsiveness with a time constant of ∼200 seconds, but tip sensitivity recovered more slowly with a time constant of ∼680 seconds. Dialysis of 5 mM NADPH into the rod promoted an earlier recovery and eliminated the previously observed tip/base difference. Dialysis of 1.66 mM NADPH failed to eliminate the tip/base recovery difference, suggesting the steady-state NADPH concentration in rods is ∼1 mM. These results indicate the inner segment is the primary source of reducing equivalents after pigment bleaching, with the reduction of all-trans retinal to all-trans retinol playing a key step in the recovery of sensitivity.

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 rdgE: A Novel Retinal Degeneration Mutation in Drosophila melanogaster

Genetics ◽  
1996 ◽  
Vol 144 (1) ◽  
pp. 127-138
Author(s):  
Troy Zars ◽  
David R Hyde
Keyword(s):  
Electron Microscopy ◽  
Retinal Degeneration ◽  
Light Response ◽  
Neuronal Membrane ◽  
Constant Darkness ◽  
Multivesicular Bodies ◽  
Photoreceptor Degeneration ◽  
Transmission Electron ◽  
Phototransduction Cascade ◽  
Membrane Biosynthesis

Abstract We report isolating the Drosophila retinal degeneration E (rdgE) mutation. The hypomorphic rdgE  1 allele causes rapid photoreceptor degeneration in light and a slower rate of degeneration when the flies are raised in constant darkness. The rdgE  1 flies exhibited an electrophysiological light response that decreased with age, coinciding with the degeneration. This suggests that degeneration caused the loss of the light response. We determined that the ninaE (rhodopsin) mutation, but not norpA [phospholipase C (PLC)], slowed the rdgE-dependent degeneration. This was consistent with the light-enhanced degeneration, but revealed that the degeneration is independent of the PLC-mediated phototransduction cascade. Transmission electron microscopy revealed that rdgE  1 photoreceptors exhibited a number of vesicular transport defects including unpacking/vesiculation of rhabdomeres, endocytosis of novel vesicles by photoreceptors, a buildup of very large multivesicular bodies, and an increased amount of rough endoplasmic reticulum. We determined that the rdgE null phenotype is a late embryonic lethality. Therefore, rdgE  + is required in cells outside of the retina, quite possibly in a large number of neurons. Thus, rdgE may define a mutational class that exhibits both light-enhanced retinal degeneration and a recessive null lethality by perturbing neuronal membrane biosynthesis and/or recycling.

scholarly journals Kinetics of Recovery of the Dark-adapted Salamander Rod Photoresponse

1998 ◽  
Vol 111 (1) ◽  
pp. 7-37 ◽  
Author(s):  
S. Nikonov ◽  
N. Engheta ◽  
E.N. Pugh
Keyword(s):  
Theoretical Analysis ◽  
Time Constant ◽  
Translation Invariance ◽  
Flash Intensity ◽  
Translation Invariant ◽  
Calcium Dependent ◽  
The Difference ◽  
Analytical Expressions ◽  
Kinetics Of ◽  
Flash Response

The kinetics of the dark-adapted salamander rod photocurrent response to flashes producing from 10 to 105 photoisomerizations (Φ) were investigated in normal Ringer's solution, and in a choline solution that clamps calcium near its resting level. For saturating intensities ranging from ∼102 to 104 Φ, the recovery phases of the responses in choline were nearly invariant in form. Responses in Ringer's were similarly invariant for saturating intensities from ∼103 to 104 Φ. In both solutions, recoveries to flashes in these intensity ranges translated on the time axis a constant amount (τc) per e-fold increment in flash intensity, and exhibited exponentially decaying “tail phases” with time constant τc. The difference in recovery half-times for responses in choline and Ringer's to the same saturating flash was 5–7 s. Above ∼104 Φ, recoveries in both solutions were systematically slower, and translation invariance broke down. Theoretical analysis of the translation-invariant responses established that τc must represent the time constant of inactivation of the disc-associated cascade intermediate (R*, G*, or PDE*) having the longest lifetime, and that the cGMP hydrolysis and cGMP-channel activation reactions are such as to conserve this time constant. Theoretical analysis also demonstrated that the 5–7-s shift in recovery half-times between responses in Ringer's and in choline is largely (4–6 s) accounted for by the calcium-dependent activation of guanylyl cyclase, with the residual (1–2 s) likely caused by an effect of calcium on an intermediate with a nondominant time constant. Analytical expressions for the dim-flash response in calcium clamp and Ringer's are derived, and it is shown that the difference in the responses under the two conditions can be accounted for quantitatively by cyclase activation. Application of these expressions yields an estimate of the calcium buffering capacity of the rod at rest of ∼20, much lower than previous estimates.

Inhibitors of guanylate cyclase inhibit phototransduction in Limulus ventral photoreceptors

2001 ◽  
Vol 18 (4) ◽  
pp. 625-632 ◽  
Author(s):  
ALEX GARGER ◽  
EDWIN A. RICHARD ◽  
JOHN E. LISMAN
Keyword(s):  
Guanylate Cyclase ◽  
Light Response ◽  
Substantial Effect ◽  
Membrane Properties ◽  
Soluble Form ◽  
Similar Reduction ◽  
Excised Patches ◽  
Oxide Synthase ◽  
Phototransduction Cascade ◽  
Reversible Reduction

The second messenger systems involved in the final stages of the phototransduction cascade in Limulus photoreceptors remain unclear. Excised patches of transducing membrane contain cGMP-gated channels, suggesting the involvement of cGMP in the excitation process. To further explore this possibility, we tested the effects of inhibitors and agonists of guanylate cyclase. The active site cyclase inhibitors guanosine 5′-tetraphosphate and adenosine 5′-tetraphosphate produced a reversible reduction of the response to light without affecting resting membrane properties. The cyclase inhibitor Rp-GTPαS produced a similar reduction, but the effect was only slightly reversible. The reduction in the response produced by these inhibitors was robust, often producing over a 95% decrease in the amplitude of the light response. Previous work had shown that an end-product cyclase inhibitor, imidodiphosphate, also inhibited the response. The consistent results with four different guanylate cyclase inhibitors strongly support the involvement of this enzyme in the phototransduction cascade. To determine whether the guanylate cyclase involved is the NO-dependent soluble form, we applied inhibitors and activators of the nitric oxide synthase/guanylate cyclase pathway such as L-N5-(1-iminoethyl) ornithine, sodium nitroprusside, and carboxy-PTIO. None of these agents had any substantial effect on phototransduction. Taken together, these results support a role for a particulate guanylate cyclase in Limulus photoreceptor excitation.

scholarly journals The kinetics of inactivation of the rod phototransduction cascade with constant Ca2+i.

1996 ◽  
Vol 107 (1) ◽  
pp. 19-34 ◽  
Author(s):  
A Lyubarsky ◽  
S Nikonov ◽  
E N Pugh
Keyword(s):  
G Protein ◽  
Time Constant ◽  
Inactivation Kinetics ◽  
First Order ◽  
Successful Model ◽  
Ringer’S Solution ◽  
Rhodopsin Kinase ◽  
Solution Bathing ◽  
Kinetics Of ◽  
Phototransduction Cascade

A rich variety of mechanisms govern the inactivation of the rod phototransduction cascade. These include rhodopsin phosphorylation and subsequent binding of arrestin; modulation of rhodopsin kinase by S-modulin (recoverin); regulation of G-protein and phosphodiesterase inactivation by GTPase-activating factors; and modulation of guanylyl cyclase by a high-affinity Ca(2+)-binding protein. The dependence of several of the inactivation mechanisms on Ca2+i makes it difficult to assess the contributions of these mechanisms to the recovery kinetics in situ, where Ca2+i is dynamically modulated during the photoresponse. We recorded the circulating currents of salamander rods, the inner segments of which are held in suction electrodes in Ringer's solution. We characterized the response kinetics to flashes under two conditions: when the outer segments are in Ringer's solution, and when they are in low-Ca2+ choline solutions, which we show clamp Ca2+i very near its resting level. At T = 20-22 degrees C, the recovery phases of responses to saturating flashes producing 10(2.5)-10(4.5) photoisomerizations under both conditions are characterized by a dominant time constant, tau c = 2.4 +/- 0.4 s, the value of which is not dependent on the solution bathing the outer segment and therefore not dependent on Ca2+i. We extended a successful model of activation by incorporating into it a first-order inactivation of R*, and a first-order, simultaneous inactivation of G-protein (G*) and phosphodiesterase (PDE*). We demonstrated that the inactivation kinetics of families of responses obtained with Ca2+i clamped to rest are well characterized by this model, having one of the two inactivation time constants (tau r* or tau PDE*) equal to tau c, and the other time constant equal to 0.4 +/- 0.06 s.

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.

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