Italian National Research Council, Istituto di Scienze del Patrimonio Culturale, Roma, Italy.
The Mathematical Biosciences Institute, Ohio State University, Columbus, OH, United States of America.
PLoS One. 2020 Oct 14;15(10):e0240527. doi: 10.1371/journal.pone.0240527. eCollection 2020.
Retinal rods function as accurate photon counters to provide for vision under very dim light. To do so, rods must generate highly amplified, reproducible responses to single photons, yet outer segment architecture and randomness in the location of rhodopsin photoisomerization on the surface of an internal disk introduce variability to the rising phase of the photon response. Soon after a photoisomerization at a disk rim, depletion of cGMP near the plasma membrane closes ion channels and hyperpolarizes the rod. But with a photoisomerization in the center of a disk, local depletion of cGMP is distant from the channels in the plasma membrane. Thus, channel closure is delayed by the time required for the reduction of cGMP concentration to reach the plasma membrane. Moreover, the local fall in cGMP dissipates over a larger volume before affecting the channels, so response amplitude is reduced. This source of variability increases with disk radius. Using a fully space-resolved biophysical model of rod phototransduction, we quantified the variability attributable to randomness in the location of photoisomerization as a function of disk structure. In mouse rods that have small disks bearing a single incisure, this variability was negligible in the absence of the incisure. Variability was increased slightly by the incisure, but randomness in the shutoff of rhodopsin emerged as the main source of single photon response variability at all but the earliest times. Variability arising from randomness in the transverse location of photoisomerization increased in magnitude and persisted over a longer period in the photon response of large salamander rods. A symmetric arrangement of multiple incisures in the disks of salamander rods greatly reduced this variability during the rising phase, but the incisures had the opposite effect on variability arising from randomness in rhodopsin shutoff at later times.
视杆细胞作为精确的光子计数器，在非常昏暗的光线下提供视觉。为此，视杆细胞必须对单个光子产生高度放大、可重复的响应，然而，外段结构和视紫红质光异构化在内部盘表面的位置上的随机性，给光子响应的上升相带来了可变性。在盘缘的光异构化后不久，靠近质膜的 cGMP 的耗竭关闭离子通道并使视杆细胞超极化。但是，在盘的中心发生光异构化时，cGMP 的局部耗竭远离质膜中的通道。因此，通道关闭的时间取决于 cGMP 浓度降低到达质膜所需的时间。此外，cGMP 的局部下降在影响通道之前会在更大的体积中消散，因此响应幅度会降低。这种可变性的来源随盘半径的增加而增加。使用视杆细胞光转导的完全空间分辨生物物理模型，我们定量了由于光异构化位置的随机性引起的可变性，作为盘结构的函数。在具有带有单个切痕的小盘的小鼠视杆细胞中，在不存在切痕的情况下，这种可变性可以忽略不计。切痕略微增加了可变性，但在所有情况下，除了最早的时间外，视紫红质关闭的随机性成为单光子响应可变性的主要来源。光异构化的横向位置随机性引起的可变性在幅度上增加，并在大蝾螈视杆细胞的光子响应中持续更长时间。蝾螈视杆细胞盘上多个切痕的对称排列在上升相期间大大降低了这种可变性，但切痕对后期视紫红质关闭随机性引起的可变性产生了相反的影响。
