Analysis of waveform and amplitude of mouse rod and cone flash responses

Abtout, Annia; Fain, Gordon; Reingruber, Jürgen

doi:10.1113/jp281225

Cited by 5 publications

(14 citation statements)

References 57 publications

(109 reference statements)

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“…Moreover, since for we have , we obtain . Thus, for large μ ca we obtain that the Ca 2+ concentration changes in proportion to the current, and we recover our results from [15, 16]. We now generalize our previous results by studying how electrical current and Ca 2+ dynamics are affected if the rate μ ca decreases, for example, due to increased buffering or treatment with the calcium buffer BAPTA.…”

Section: Methodssupporting

confidence: 81%

“…Since many of these steps depend on Ca 2+ feedback, it is important to understand how the dynamics of the free Ca 2+ concentration affects the photoresponse. In previous work, we analysed the dim-light response assuming that the free Ca 2+ concentration changes in proportion to the current [15, 16]. In this present work, we generalized our previous results by considering the effect of buffering, which can delay the Ca 2+ dynamics with respect to the current.…”

Section: Discussionmentioning

confidence: 66%

“…3 reduces to a model where the free- Ca 2+ concentration changes in proportion to the current, . We previously analysed and calibrated such a model using dim-flash recordings for mouse WT and GCAPs -/- rods and cones [15, 16]. We now use these parameters to study how the photoresponse changes as the value of μ ca decreases, for example, due to increased buffering.…”

Section: Resultsmentioning

confidence: 99%

“…We use a spatially homogeneous signal transduction model for the outer segment (OS) similar to one previously described [16,15] (see also [21,19,22,20,23]). In brief, light illumination generates activated visual pigment R * with a rate that is proportional to the light intensity φ(t) times the collecting area κ. R * deactivates with a rate µ rh and generates the activated G-protein transducin T * with a rate k act .…”

Section: Phototransduction Modelmentioning

confidence: 99%

“…To derive analytic results that provide quantitative insight, we use a spatially well-stirred phototransduction model that comprises the most relevant phototransduction steps [15]. In previous work, we analysed this model with the approximation that the free- Ca 2+ concentration changes in proportion to the circulating current [15, 16]. Since however there is uncertainty about the degree of Ca 2+ buffering in mouse rods and cones [17, 18, 19, 20], it is unclear how our previous results change if the Ca 2+ dynamics becomes delayed with respect to the current, for example due to increased buffering.…”

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: Methodssupporting

confidence: 81%

Section: Discussionmentioning

confidence: 66%

Section: Resultsmentioning

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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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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Molecular bases of rod and cone differences

Kawamura

Tachibanaki

2022

Progress in Retinal and Eye Research

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Analysis of waveform and amplitude of mouse rod and cone flash responses

Cited by 5 publications

References 57 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

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

Molecular bases of rod and cone differences

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