scholarly journals cAMP controls rod photoreceptor sensitivity via multiple targets in the phototransduction cascade

2012 ◽  
Vol 140 (4) ◽  
pp. 421-433 ◽  
Author(s):  
Luba A. Astakhova ◽  
Evgeniia V. Samoiliuk ◽  
Victor I. Govardovskii ◽  
Michael L. Firsov

In early studies, both cyclic AMP (cAMP) and cGMP were considered as potential secondary messengers regulating the conductivity of the vertebrate photoreceptor plasma membrane. Later discovery of the cGMP specificity of cyclic nucleotide–gated channels has shifted attention to cGMP as the only secondary messenger in the phototransduction cascade, and cAMP is not considered in modern schemes of phototransduction. Here, we report evidence that cAMP may also be involved in regulation of the phototransduction cascade. Using a suction pipette technique, we recorded light responses of isolated solitary rods from the frog retina in normal solution and in the medium containing 2 µM of adenylate cyclase activator forskolin. Under forskolin action, flash sensitivity rose more than twofold because of a retarded photoresponse turn-off. The same concentration of forskolin lead to a 2.5-fold increase in the rod outer segment cAMP, which is close to earlier reported natural day/night cAMP variations. Detailed analysis of cAMP action on the phototransduction cascade suggests that several targets are affected by cAMP increase: (a) basal dark phosphodiesterase (PDE) activity decreases; (b) at the same intensity of light background, steady background-induced PDE activity increases; (c) at light backgrounds, guanylate cyclase activity at a given fraction of open channels is reduced; and (d) the magnitude of the Ca2+ exchanger current rises 1.6-fold, which would correspond to a 1.6-fold elevation of [Ca2+]in. Analysis by a complete model of rod phototransduction suggests that an increase of [Ca2+]in might also explain effects (b) and (c). The mechanism(s) by which cAMP could regulate [Ca2+]in and PDE basal activity is unclear. We suggest that these regulations may have adaptive significance and improve the performance of the visual system when it switches between day and night light conditions.

1987 ◽  
Vol 130 (1) ◽  
pp. 259-274
Author(s):  
MAKOTO MIZUNAMI ◽  
SHIGEKI YAMASHITA ◽  
HIDEKI TATEDA

The ionic basis of the action potential in the large second-order neurones (L-neurones) of the ocellus of the cockroach, Periplaneta americana, was studied. L-neurones generated action potentials, usually once, at the off-set of hyperpolarizing light responses, or at the termination of hyperpolarizing current stimuli. The action potential was blocked by replacing saline Ca2+ with Mg2+ but maintained when Ba2+ was substituted. A block was produced by 2 mmoll l−1 Cd2+ or 20 mmol l−l Co2+. The peak amplitude of the action potential increased by 26 mV for a 10-fold increase in external Ca2+ concentration, at concentrations below 1.8 mmol l−1. The action potential was not affected by sodium-free saline or by 3×10−6mol l−1 tetrodotoxin (TTX). These observations suggest that calcium ions are the major carrier for the inward current of the action potential. This finding supports the suggestion that the off-set responses of hyperpolarizing visual neurones of both vertebrates and invertebrates have a common ionic mechanism, including voltage-sensitive calcium currents.


2010 ◽  
Vol 135 (4) ◽  
pp. 355-366 ◽  
Author(s):  
Hugh R. Matthews ◽  
Alapakkam P. Sampath

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.


2019 ◽  
Author(s):  
Cagney E. Coomer ◽  
Stephen G. Wilson ◽  
Kayla F. Titialii-Torres ◽  
Jessica D. Bills ◽  
Laura A. Krueger ◽  
...  

AbstractThe intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange (bHLH-O) transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased numbers of rods and red/green cones, whereas blue and UV cones were relatively unaffected. The reduction in rods and red/green cones correlated with defects in photoreceptor subtype lineage specification. The remaining rods and double cones displayed abnormally truncated outer segments, and elevated levels of apoptosis. In addition to the photoreceptor defects, her9 mutants also possessed a reduced proliferative ciliary marginal zone, and decreased and disorganized Müller glia. Mutation of her9 was larval lethal, with no mutants surviving past 13 days post fertilization. Our results reveal a previously undescribed role for Her9/Hes4 in photoreceptor differentiation, maintenance, and survival.


1997 ◽  
Vol 17 (23) ◽  
pp. 9068-9076 ◽  
Author(s):  
Elena Molokanova ◽  
Bhavya Trivedi ◽  
Alexei Savchenko ◽  
Richard H. Kramer

1998 ◽  
Vol 142 (2) ◽  
pp. 473-484 ◽  
Author(s):  
Burkhard Wiesner ◽  
Jocelyn Weiner ◽  
Ralf Middendorff ◽  
Volker Hagen ◽  
U. Benjamin Kaupp ◽  
...  

Cyclic nucleotide-gated (CNG) channels are key elements of cGMP- and cAMP-signaling pathways in vertebrate photoreceptor cells and in olfactory sensory neurons, respectively. These channels form heterooligomeric complexes composed of at least two distinct subunits (α and β). The α subunit of cone photoreceptors is also present in mammalian sperm. Here we identify one short and several long less abundant transcripts of β subunits in testis. The α and β subunits are expressed in a characteristic temporal and spatial pattern in sperm and precursor cells. In mature sperm, the α subunit is observed along the entire flagellum, whereas the short β subunit is restricted to the principal piece of the flagellum. These findings suggest that different forms of CNG channels coexist in the flagellum. Confocal microscopy in conjunction with the Ca2+ indicator Fluo-3 shows that the CNG channels serve as a Ca2+ entry pathway that responds more sensitively to cGMP than to cAMP. Assuming that CNG channel subtypes differ in their Ca2+ permeability, dissimilar localization of α and β subunits may give rise to a pattern of Ca2+ microdomains along the flagellum, thereby providing the structural basis for control of flagellar bending waves.


2020 ◽  
Vol 117 (32) ◽  
pp. 19599-19603
Author(s):  
Norianne T. Ingram ◽  
Gordon L. Fain ◽  
Alapakkam P. Sampath

We have used recent measurements of mammalian cone light responses and voltage-gated currents to calculate cone ATP utilization and compare it to that of rods. The largest expenditure of ATP results from ion transport, particularly from removal of Na+entering outer segment light-dependent channels and inner segment hyperpolarization-activated cyclic nucleotide-gated channels, and from ATP-dependent pumping of Ca2+entering voltage-gated channels at the synaptic terminal. Single cones expend nearly twice as much energy as single rods in darkness, largely because they make more synapses with second-order retinal cells and thus must extrude more Ca2+. In daylight, cone ATP utilization per cell remains high because cones never remain saturated and must continue to export Na+and synaptic Ca2+even in bright illumination. In mouse and human retina, rods greatly outnumber cones and consume more energy overall even in background light. In primates, however, the high density of cones in the fovea produces a pronounced peak of ATP utilization, which becomes particularly prominent in daylight and may make this part of the retina especially sensitive to changes in energy availability.


1996 ◽  
Vol 109 (7) ◽  
pp. 1803-1812
Author(s):  
M.A. Hallett ◽  
J.L. Delaat ◽  
K. Arikawa ◽  
C.L. Schlamp ◽  
F. Kong ◽  
...  

Guanylate cyclases play an essential role in the recovery of vertebrate photoreceptor cells after light activation. Here, we have investigated how one such guanylate cyclase, RetGC-1, is distributed within light- and dark-adapted rod photoreceptor cells. Guanylate cyclase activity partitioned with the photoreceptor outer segment (OS) cytoskeleton in a light-sensitive manner. RetGC-1 was found to bind actin filaments in actin blot overlays, suggesting a mechanism for its association with the OS cytoskeleton. In retinal sections, this enzyme was immunodetected only in the OSs, where it appeared to be distributed throughout the disk membranes.


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