Longitudinal diffusion in retinal rod and cone outer segment cytoplasm: The consequence of cell structure
Longitudinal diffusion in retinal rod and cone outer segment cytoplasm: The consequence of cell structure
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DOI：
10.1016/s0006-3495(04)74312-x
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发表时间：
2004-04-01
影响因子：
3.4
通讯作者：
Korenbrot, JI
中科院分区：
文献类型：
--
作者：
Holcman, D;Korenbrot, JI
由于细胞质第二信使 cGMP 的纵向扩散，激发信号沿光感受器外节传播，远离光子捕获位点。纵向扩散的定量特征反映了外节的解剖结构，已知杆状光感受器和锥状光感受器有很大不同。为了探索结构差异如何影响细胞质扩散并评估纵向扩散是否可能导致光感受器类型之间信号转导的差异，我们从理论上和实验上研究了外部节段中亲水性小分子的纵向扩散。我们开发了一种新的理论分析来明确计算外段结构方面的纵向扩散常数 D-1。使用时间分辨荧光成像，我们测量了完整的单视锥细胞中 Alexa488 的 D-1 和荧光黄，并验证了理论分析。我们使用理论模型的数值模拟来研究不同物种外节中的 cGMP 扩散。在给定的时间间隔内，cGMP 在杆中比在相同尺寸的锥外段中传播得更远。在所有物种中，在弱光光电流峰值处，cGMP 的空间分布在视杆外节中为 3-5 μm，无论其绝对大小如何。类似地，cGMP 空间分布在圆锥外段中为 0.7-1 μm，与其尺寸无关。
Excitation signals spread along photoreceptor outer segments away from the site of photon capture because of longitudinal diffusion of cGMP, a cytoplasmic second messenger. The quantitative features of longitudinal diffusion reflect the anatomical structure of the outer segment, known to be profoundly different in rod and cone photoreceptors. To explore how structural differences affect cytoplasmic diffusion and to assess whether longitudinal diffusion may contribute to the difference in signal transduction between photoreceptor types, we investigated, both theoretically and experimentally, the longitudinal diffusion of small, hydrophilic molecules in outer segments. We developed a new theoretical analysis to explicitly compute the longitudinal diffusion constant, D-1, in terms of outer segment structure. Using time-resolved fluorescence imaging we measured D-1 of Alexa488 and lucifer yellow in intact, single cones and validated the theoretical analysis. We used numerical simulations of the theoretical model to investigate cGMP diffusion in outer segments of various species. At a given time interval, cGMP spreads further in rod than in cone outer segments of the same dimensions. Across all species, the spatial spread of cGMP at the peak of the dim light photocurrent is 3-5 mum in rod outer segments, regardless of their absolute size. Similarly the cGMP spatial spread is 0.7-1 mum in cone outer segments, independently of their dimensions.