Code and simulated data from A quantitative account of mammalian rod phototransduction with PDE6 dimeric activation: responses to bright flashes

We develop an improved quantitative model of mammalian rod phototransduction, and we apply it to the prediction of responses to bright flashes of light. We take account of the recently characterized dimeric nature of PDE6 activation, where the configuration of primary importance has two transducin molecules bound. We simulate the stochastic nature of the activation and shut-off reactions, to generate the predicted kinetics of the active molecular species on the disc membrane surfaces, and then we integrate the differential equations for the downstream cytoplasmic reactions to obtain the predicted electrical responses. The simulated responses recover the qualitative form of bright-flash response families recorded from mammalian rod photoreceptors. Furthermore, they provide an accurate description of the relationship between the time spent in saturation and flash intensity, predicting the transition between first and second ‘dominant time constants’ to occur at an intensity around 5000 isomerizations per flash, when the rate of transducin activation is taken to be 1250 transducins s⁻¹ per activated rhodopsin. This rate is consistent with estimates from light-scattering experiments, but is around fourfold higher than has typically been assumed in other studies. We conclude that our model and parameters provide a compelling description of rod photoreceptor bright-flash responses.

本研究构建了一种改进的哺乳动物视杆细胞光转导定量模型，并将其用于强光闪光响应的预测。本研究考量了近期解析的磷酸二酯酶6（PDE6）激活的二聚体特性，其中核心构型为结合两个转导蛋白（Transducin）分子的状态。我们模拟了激活与失活反应的随机特性，以生成盘膜表面活性分子物种的预测动力学曲线；随后对下游胞质反应的微分方程进行数值积分，得到预测的电响应。模拟所得的响应复现了从哺乳动物视杆光感受器中记录的强光闪光响应家族的定性特征。此外，该模型准确描述了饱和持续时间与闪光强度之间的关联，当转导蛋白激活速率设定为每个激活的视紫红质（Rhodopsin）每秒1250个转导蛋白时，预测第一与第二‘主导时间常数’之间的转换发生在单次闪光约5000次光异构化的强度处。该激活速率与光散射实验的估算结果相符，但比其他研究中的常规假设值高出约四倍。综上，本研究的模型与参数能够令人信服地描述视杆光感受器的强光闪光响应。