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.

scholarly journals Evolution and the origin of the visual retinoid cycle in vertebrates

2009 ◽  
Vol 364 (1531) ◽  
pp. 2897-2910 ◽  
Author(s):  
Takehiro G. Kusakabe ◽  
Noriko Takimoto ◽  
Minghao Jin ◽  
Motoyuki Tsuda
Keyword(s):  
Visual Pigment ◽  
Photoreceptor Cells ◽  
Light Sensitivity ◽  
Visual Cycle ◽  
Interphotoreceptor Retinoid Binding Protein ◽  
New Genes ◽  
Ascidian Larva ◽  
Cycle Systems ◽  
Subcellular Compartmentalization ◽  
Cellular Compartments

Absorption of a photon by visual pigments induces isomerization of 11- cis -retinaldehyde (RAL) chromophore to all- trans -RAL. Since the opsins lacking 11- cis -RAL lose light sensitivity, sustained vision requires continuous regeneration of 11- cis -RAL via the process called ‘visual cycle’. Protostomes and vertebrates use essentially different machinery of visual pigment regeneration, and the origin and early evolution of the vertebrate visual cycle is an unsolved mystery. Here we compare visual retinoid cycles between different photoreceptors of vertebrates, including rods, cones and non-visual photoreceptors, as well as between vertebrates and invertebrates. The visual cycle systems in ascidians, the closest living relatives of vertebrates, show an intermediate state between vertebrates and non-chordate invertebrates. The ascidian larva may use retinochrome-like opsin as the major isomerase. The entire process of the visual cycle can occur inside the photoreceptor cells with distinct subcellular compartmentalization, although the visual cycle components are also present in surrounding non-photoreceptor cells. The adult ascidian probably uses RPE65 isomerase, and trans -to- cis isomerization may occur in distinct cellular compartments, which is similar to the vertebrate situation. The complete transition to the sophisticated retinoid cycle of vertebrates may have required acquisition of new genes, such as interphotoreceptor retinoid-binding protein, and functional evolution of the visual cycle genes.

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 The V-ATPase V1 subunit A1 is required for rhodopsin anterograde trafficking in Drosophila

2018 ◽  
Vol 29 (13) ◽  
pp. 1640-1651 ◽  
Author(s):  
Haifang Zhao ◽  
Jing Wang ◽  
Tao Wang
Keyword(s):  
Animal Model ◽  
Endoplasmic Reticulum ◽  
Secretory Pathway ◽  
Photoreceptor Cell ◽  
Photoreceptor Cells ◽  
Secretory Vesicle ◽  
Light Sensitivity ◽  
Model System ◽  
Genetic Screen ◽  
Reduced Light

Synthesis and maturation of the light sensor, rhodopsin, are critical for the maintenance of light sensitivity and for photoreceptor homeostasis. In Drosophila, the main rhodopsin, Rh1, is synthesized in the endoplasmic reticulum and transported to the rhabdomere through the secretory pathway. In an unbiased genetic screen for factors involved in rhodopsin homeostasis, we identified mutations in vha68-1, which encodes the vacuolar proton-translocating ATPase (V-ATPase) catalytic subunit A isoform 1 of the V1 component. Loss of vha68-1 in photoreceptor cells disrupted post-Golgi anterograde trafficking of Rh1, reduced light sensitivity, increased secretory vesicle pH, and resulted in incomplete Rh1 deglycosylation. In addition, vha68-1 was required for activity-independent photoreceptor cell survival. Importantly, vha68-1 mutants exhibited phenotypes similar to those exhibited by mutations in the V0 component of V-ATPase, vha100-1. These data demonstrate that the V1 and V0 components of V-ATPase play key roles in post-Golgi trafficking of Rh1 and that Drosophila may represent an important animal model system for studying diseases associated with V-ATPase dysfunction.

scholarly journals Transduction persists in rod photoreceptors after depletion of intracellular calcium.

1987 ◽  
Vol 89 (2) ◽  
pp. 297-319 ◽  
Author(s):  
G D Nicol ◽  
U B Kaupp ◽  
M D Bownds
Keyword(s):  
Cyclic Gmp ◽  
Dark Current ◽  
Phosphodiesterase Inhibitor ◽  
Light Regulation ◽  
Response Duration ◽  
Light Sensitivity ◽  
Ionophore A23187 ◽  
Active Suspensions ◽  
Rod Photoreceptors ◽  
Intracellular Ca

We have examined the role of Ca++ in phototransduction by manipulating the intracellular Ca++ concentration in physiologically active suspensions of isolated and purified rod photoreceptors (OS-IS). The results are summarized by the following. Measurement of Ca++ content using arsenazo III spectroscopy demonstrates that incubation of OS-IS in 10 nM Ca++-Ringer's solution containing the Ca++ ionophore A23187 reduces their Ca++ content by 93%, from 1.3 to 0.1 mol Ca++/mol rhodopsin. Virtually the same reduction can be accomplished in 10 nM Ca++-Ringer's without ionophore, presumably via the plasma membrane Na/Ca exchange mechanism. Hundreds of photoresponses can be obtained from the Ca++-depleted OS-IS for at least 1 h in 10 nM Ca++-Ringer's with ionophore. The kinetics and light sensitivity of the photoresponse are essentially the same in the presence or absence of the ionophore in 10 nM Ca++. The addition of A23187 in 1 mM Ca++-Ringer's results in a Ca++ influx that rapidly suppresses the dark current and the photoresponse. This indicates that there is an intracellular site at which Ca++ can modulate the light-regulated conductance. Both the current and photoresponse can be restored if intracellular Ca++ is reduced by lowering the external Ca++ to 10 nM. During the transition from high to low Ca++, the response duration becomes shorter, which suggests that it can be regulated by a Ca++-dependent mechanism. If the dark current and the photoresponse are suppressed by adding A23187 in 1 mM Ca++-Ringer's, the subsequent addition of the cyclic GMP phosphodiesterase inhibitor isobutylmethylxanthine can restore the current and photoresponse. This implies that under conditions where the rod can no longer control its intracellular Ca++, the elevation of cyclic GMP levels can restore light regulation of the channels. The persistence of normal flash responses under conditions where intracellular Ca++ levels are reduced and perturbed suggests that changes in the intracellular Ca++ concentration do not cause the closure of the light-regulated channel.

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.

Photoreceptor cells with unusual functional properties on the ventral nerve of Limulus

1999 ◽  
Vol 16 (6) ◽  
pp. 1191-1197 ◽  
Author(s):  
KÁROLY NAGY ◽  
MARLIES DORLÖCHTER ◽  
SVENJA KLÄSEN ◽  
DANNY STEINBUSCH
Keyword(s):  
Time Course ◽  
Single Photon ◽  
Receptor Potential ◽  
Photoreceptor Cells ◽  
Light Sensitivity ◽  
Atpase Inhibitor ◽  
Decay Kinetics ◽  
Normal Cells ◽  
Inward Current ◽  
Low Efficiency

Normal photoreceptor cells on the ventral nerve of Limulus respond to a moderately intense flash with a large receptor potential or current. Occasionally, cells are found in which the same flash evokes only a small receptor potential or current. Our investigations reveal physiological reasons for the poor light sensitivity in these “unusual cells.” In unusual cells prolonged illumination with intense light evokes a step-like inward current with an amplitude of some nanoamperes, but without a large transient peak. The current appears to be summed up of single photon responses with amplitudes smaller than about 50 pA. Their time course is similar to that of small single photon responses forming the so-called macroscopic C1 component in normal cells. The macroscopic current evoked by an intense flash has slow activation and deactivation kinetics and reaches a saturated amplitude of about 4–5 nanoamperes. The light-intensity dependence of the current evoked by flashes or by prolonged illumination has a slope of about 1 in log–log plots. The decay kinetics of the current is similar to that of the C1 component measured in normal cells after the block of the C2 component. Occasionally, the step-like current is superposed by large standard bumps. These bumps are blocked by the Ca2+-ATPase inhibitor cyclopiazonic acid, while the sustained inward current persists. We conclude that in unusual cells the light-activated current is identical to the C1 component of normal cells. The phospholipase C pathway that in normal cells presumably gives rise to the C2 component functions only with a low efficiency in unusual cells.

Positive and Negative Potential Responses associated with Vertebrate Photoreceptor Cells

Nature ◽  
1965 ◽  
Vol 206 (4984) ◽  
pp. 626-627 ◽  
Author(s):  
ALEXANDER BORTOFF ◽  
ALAN L. NORTON
Keyword(s):  
Photoreceptor Cells ◽  
Negative Potential ◽  
Vertebrate Photoreceptor
Sign in / Sign up

Export Citation Format

Share Document