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人视杆光转导激活与失活的简化模型:视网膜电图研究。

A Simplified Model of Activation and Deactivation of Human Rod Phototransduction-An Electroretinographic Study.

机构信息

Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States.

Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.

出版信息

Invest Ophthalmol Vis Sci. 2023 Sep 1;64(12):36. doi: 10.1167/iovs.64.12.36.

DOI:10.1167/iovs.64.12.36
PMID:37738060
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10528468/
Abstract

PURPOSE

To test the hypothesis that a simple model having properties consistent with activation and deactivation in the rod approximates the whole time course of the photoresponse.

METHODS

Routinely, an exponential of the form f = α·(1 - exp(-(τ·(t - teff)s-1))), with amplitude α, rate constant τ (often scaled by intensity), irreducible delay teff, and time exponent s-1, is fit to the early period of the flash electroretinogram. Notably, s (an integer) represents the three integrating stages in the rod amplification cascade (rhodopsin isomerization, transducin activation, and cGMP hydrolysis). The time course of the photoresponse to a 0.17 cd·s·m-2 conditioning flash (CF) was determined in 21 healthy eyes by presenting the CF plus a bright probe flash (PF) in tandem, separated by interstimulus intervals (ISIs) of 0.01 to 1.4 seconds, and calculating the proportion of the PF a-wave suppressed by the CF at each ISI. To test if similar kinetics describe deactivation, difference of exponential (DoE) functions with common α and teff parameters, respective rate constants for the initiation (I) and quenching (Q) phases of the response, and specified values of s (sI, sQ), were compared to the photoresponse time course.

RESULTS

As hypothesized, the optimal values of sI and sQ were 3 and 2, respectively. Mean ± SD α was 0.80 ± 0.066, I was 7700 ± 2400 m2·cd-1·s-3, and Q was 1.4 ± 0.47 s-1. Overall, r2 was 0.93.

CONCLUSIONS

A method, including a DoE model with just three free parameters (α, I, Q), that robustly captures the magnitude and time-constants of the complete rod response, was produced. Only two steps integrate to quench the rod photoresponse.

摘要

目的

验证一个简单的模型,该模型具有激活和失活的特性,近似于光反应的整个时间过程。

方法

通常,采用指数形式 f = α·(1 - exp(-(τ·(t - teff)s-1))) 来拟合闪光视网膜电图的早期阶段,其中幅度 α、速率常数 τ(通常按强度缩放)、不可约延迟 teff 和时间指数 s-1。值得注意的是,s(整数)代表视杆放大级联中的三个积分阶段(视紫红质异构化、转导蛋白激活和 cGMP 水解)。通过在串联呈现条件闪光 (CF) 和明亮的探测闪光 (PF),并在刺激间隔 (ISI) 为 0.01 到 1.4 秒之间,确定了 21 只健康眼睛对 0.17 cd·s·m-2 条件闪光 (CF) 的光反应时间过程,并计算了 CF 在每个 ISI 下对 PF a 波的抑制比例。为了测试是否类似的动力学描述失活,具有共同的 α 和 teff 参数、响应的起始 (I) 和猝灭 (Q) 阶段的各自速率常数以及指定的 s 值 (sI、sQ) 的指数差 (DoE) 函数被用来与光反应时间过程进行比较。

结果

正如假设的那样,sI 和 sQ 的最佳值分别为 3 和 2。平均 ± SD 的 α 值为 0.80 ± 0.066,I 为 7700 ± 2400 m2·cd-1·s-3,Q 为 1.4 ± 0.47 s-1。总的来说,r2 为 0.93。

结论

开发了一种方法,包括一个具有三个自由参数(α、I、Q)的 DoE 模型,该模型能够可靠地捕获完整视杆反应的幅度和时间常数。只有两个步骤集成来猝灭视杆光反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/cc56754e36b9/iovs-64-12-36-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/c89951cb4bfd/iovs-64-12-36-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/ac6c333b1d2f/iovs-64-12-36-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/7e6507f2a10d/iovs-64-12-36-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/cc56754e36b9/iovs-64-12-36-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/c89951cb4bfd/iovs-64-12-36-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/ac6c333b1d2f/iovs-64-12-36-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/7e6507f2a10d/iovs-64-12-36-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b9a/10528468/cc56754e36b9/iovs-64-12-36-f004.jpg

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本文引用的文献

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