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分析钙动力学改变的视杆和视锥光感受器的弱光反应。

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

机构信息

Institute of Biology, Ecole Normale Supérieure, Paris, France.

INSERM, U1024, Paris, France.

出版信息

J Math Biol. 2023 Oct 12;87(5):69. doi: 10.1007/s00285-023-02005-4.

Abstract

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[Formula: see text] feedback. It is known that manipulating the Ca[Formula: see text] 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[Formula: see text] feedback onto the synthesis of cyclic GMP, and fast buffering reactions to alter the Ca[Formula: see text] 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[Formula: see text] feedback. With a low amount of buffering, the Ca[Formula: see text] concentration changes in proportion to the current, and responses to flashes of light are monophasic. With more buffering, the change in the Ca[Formula: see text] 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[Formula: see text] concentration affects the response.

摘要

脊椎动物视网膜中的视杆和视锥细胞是视觉的主要感觉神经元。它们通过依赖 Ca2+反馈的信号转导途径将光转化为电流。已知操纵 Ca2+动力学会影响光感受器的响应形状和灵敏度,但这些影响的确切定量仍不清楚。我们通过将数值模拟与数学分析相结合,在小鼠视网膜中解决了这个问题。我们考虑了一个简约的光转导模型,该模型将负 Ca2+反馈纳入环鸟苷酸的合成,以及快速缓冲反应来改变 Ca2+动力学。我们根据光感受器的类型,针对足够暗的光条件下光感受器的功能得出了解析结果。我们利用这些结果,深入了解响应波形和幅度如何取决于潜在的生物物理过程和 Ca2+反馈。在缓冲量较低的情况下,Ca2+浓度与电流成比例变化,对光闪烁的响应为单相。随着缓冲量的增加,Ca2+浓度的变化相对于电流会延迟,从而产生阻尼振荡和双相波形。这表明双相响应不一定是慢缓冲反应的表现。我们获得了峰值闪光幅度作为光强度函数的解析近似,这表明了光感受器的灵敏度如何取决于生物物理参数。最后,我们研究了改变细胞外 Ca2+浓度如何影响响应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be5a/10570263/4fa2318ef7b7/285_2023_2005_Fig1_HTML.jpg

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