Calcium flares and compartmentalization in rod photoreceptors

Li, Yunzhen; Falleroni, Fabio; Mortal, Simone; Bocchero, Ulisse; Cojoc, Dan; Torre, Vincent

doi:10.1073/pnas.2004909117

Cited by 5 publications

(12 citation statements)

References 45 publications

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“…We used our spatially resolved phototransduction model [19] to perform simulations that showed that our conclusions remain valid when using a spatially resolved model (not shown). Recently, it has been found that the large outer segment of frog rods is a spatially inhomogeneous compartment [6, 35]. However, no such findings exist for mouse or primate rods and cones, which we focused on in this work.…”

Section: Discussionmentioning

confidence: 95%

“…We find a maximal sensitivity ratio around 2-3 between GCAPs −/− and WT photoreceptors for fast Ca 2+ kinetics. Because the observed sensitivity ratio between GCAPs −/− and WT photoreceptors is around 3 [34, 17, 52], this suggests that under physiological conditions the Ca 2+ kinetics is fast, and that the Ca 2+ concentration changes in proportion to the current [51, 60]. For step responses with an intermediate plateau phase, oscillations are visible during the initial and recovery phase of the response (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…, where r α = α min αmax ≤ 1. The total Ca 2+ concentration in the OS comprising free and buffered Ca 2+ changes due to influx via cGMP gated CNG channels and efflux via electrogenic NCKX exchangers [4,21,24,25,18,6]. Ca 2+ binds to and regulates the activity of several enzymes of the phototransduction cascade, for example, the activity of guanylate cyclase via the association with the Ca 2+ -binding proteins GCAPs, or the rate of rhodopsin deactivation via binding to recoverin [26].…”

Section: Phototransduction Modelmentioning

confidence: 99%

“…Whereas the dynamics of the electrical current is experimentally well characterized, it remains difficult to measure the time course of the change in the free- Ca 2+ concentration in the constrained space of the outer segment. Recently the Ca 2+ -dynamics in the relatively large outer segment of amphibian rods (Xenopus frog) has been measured using a fluorescent calcium dye [6]. However, no such data is available that shows the Ca 2+ -dynamics in the much smaller outer segments of mouse or primate rods, or of cones.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of calcium dynamics for dim-light responses in rod and cone photoreceptors

Abtout

Reingruber

2022

Preprint

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Rod and cone photoreceptors in vertebrate eyes are fundamental sensory neurons underlying vision. They use a sophisticated signal transduction pathway consisting of a series of biochemical processes to convert the absorption of light into an electrical response. Several of these processes are modulated by feedback mechanisms that depend on the intracellular Ca2+ concentration. In this work we use a representative phototransduction model with fast buffering to study how the Ca2+ dynamics affects the light response of mouse rod and cone photoreceptors. We obtain analytic solutions for dim-light stimulation that reveal how the dynamics of the Ca2+ concentration and the electrical current are correlated. We show how modifying the Ca2+ dynamics via buffering affects amplitude and waveform of flash and step responses. We infer that under normal physiological conditions the change in the Ca2+ concentration is proportional to the current. We show that damped oscillations appear if the Ca2+ dynamics becomes slowed down and delayed with respect to the current, e.g. through the application of buffers. We find that oscillations do not require the presence of slow buffers. We show that the phase space of the dim-light response is controlled by the ratio between the effective rate μca that controls the Ca2+ dynamics, and the dark turnover rate of cyclic GMP βd. Finally, we investigate how the light response is affected by modifying the extracellular Ca2+ concentration. In summary, we provide a comprehensive analysis that reveals how the Ca2+ dynamics affects the dim-light response in rods and cones.SignificanceThe signal transduction pathway of vertebrate rod and cone photoreceptors transforms light into an electrical response. It is regulated by several feedback processes that depend on the intracellular Ca2+ concentration. Despite of the importance of this feedback for the photoreceptor functioning, it is not well studied how modifying the Ca2+ dynamics affects the light response, for example by adding buffers. Here we derive analytic results for dim-light stimulations that provide insight into how the Ca2+ dynamics and the electrical current response are correlated. Our analysis can be used to infer properties of the Ca2+ dynamics from the observed current response, and provides insight if direct measurements of the Ca2+ dynamics in the small outer segment of a photoreceptors are not available.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Phototransduction Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of calcium dynamics for dim-light responses in rod and cone photoreceptors

Abtout

Reingruber

2022

Preprint

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“…More precise and recent techniques such as atomic force microscopy, micropipettes, optical tweezers, magnetic tweezers, and uniaxial stretchers, have allowed great progress into mechanotransduction pathways studies (Huang et al, 2004;Chighizola et al, 2019) (Figure 5A). Amongst these methods, OT offers the advantage of being non-invasive, applying comparively large forces, being able to probe cells in a 3D scaffold environment and precisely measuring forces in 3D space (Nawaz et al, 2012;Capitanio and Pavone, 2013;Pontes et al, 2013;Arbore et al, 2019;Li et al, 2020). Very recently, Dagro et al (2019) used optically trapped silica beads to deform cell surfaces and measure their stiffness and elasticity.…”

Section: Mechanical Properties Of Neuronsmentioning

confidence: 99%

Optical Tweezers Exploring Neuroscience

Lenton

Scott

Rubinsztein‐Dunlop

et al. 2020

Front. Bioeng. Biotechnol.

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Over the past decade, optical tweezers (OT) have been increasingly used in neuroscience for studies of molecules and neuronal dynamics, as well as for the study of model organisms as a whole. Compared to other areas of biology, it has taken much longer for OT to become an established tool in neuroscience. This is, in part, due to the complexity of the brain and the inherent difficulties in trapping individual molecules or manipulating cells located deep within biological tissue. Recent advances in OT, as well as parallel developments in imaging and adaptive optics, have significantly extended the capabilities of OT. In this review, we describe how OT became an established tool in neuroscience and we elaborate on possible future directions for the field. Rather than covering all applications of OT to neurons or related proteins and molecules, we focus our discussions on studies that provide crucial information to neuroscience, such as neuron dynamics, growth, and communication, as these studies have revealed meaningful information and provide direction for the field into the future.

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Analysis of dim-light responses in rod and cone photoreceptors with altered calcium kinetics

Abtout,

Reingruber

2023

J. Math. Biol.

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Rod and cone photoreceptors in the retina of vertebrates are the primary sensory neurons underlying vision. They convert light into an electrical current using a signal transduction pathway that depends on Ca$$^{2+}$$ 2 + feedback. It is known that manipulating the Ca$$^{2+}$$ 2 + kinetics affects the response shape and the photoreceptor sensitivity, but a precise quantification of these effects remains unclear. We have approached this task in mouse retina by combining numerical simulations with mathematical analysis. We consider a parsimonious phototransduction model that incorporates negative Ca$$^{2+}$$ 2 + feedback onto the synthesis of cyclic GMP, and fast buffering reactions to alter the Ca$$^{2+}$$ 2 + kinetics. We derive analytic results for the photoreceptor functioning in sufficiently dim light conditions depending on the photoreceptor type. We exploit these results to obtain conceptual and quantitative insight into how response waveform and amplitude depend on the underlying biophysical processes and the Ca$$^{2+}$$ 2 + feedback. With a low amount of buffering, the Ca$$^{2+}$$ 2 + concentration changes in proportion to the current, and responses to flashes of light are monophasic. With more buffering, the change in the Ca$$^{2+}$$ 2 + concentration becomes delayed with respect to the current, which gives rise to a damped oscillation and a biphasic waveform. This shows that biphasic responses are not necessarily a manifestation of slow buffering reactions. We obtain analytic approximations for the peak flash amplitude as a function of the light intensity, which shows how the photoreceptor sensitivity depends on the biophysical parameters. Finally, we study how changing the extracellular Ca$$^{2+}$$ 2 + concentration affects the response.

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Calcium flares and compartmentalization in rod photoreceptors

Cited by 5 publications

References 45 publications

Analysis of calcium dynamics for dim-light responses in rod and cone photoreceptors

Analysis of calcium dynamics for dim-light responses in rod and cone photoreceptors

Optical Tweezers Exploring Neuroscience

Analysis of dim-light responses in rod and cone photoreceptors with altered calcium kinetics

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