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Longitudinal Diffusion in Retinal Rod and Cone Outer Segment Cytoplasm: The Consequence of Cell Structure

Keck Center for Theoretical Neurobiology and Department of Physiology, School of Medicine, University of California at San Francisco, San Francisco, California

Correspondence: Address reprint requests to Juan I. Korenbrot, Dept. of Physiology, School of Medicine, Box 0444, University of California at San Francisco, San Francisco, CA 94143. Tel.: 415-476-1652; Fax: 415-476-4929; E-mail: juan{at}itsa.ucsf.edu.

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_l, in terms of outer segment structure. Using time-resolved fluorescence imaging we measured D_l 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 µm in rod outer segments, regardless of their absolute size. Similarly the cGMP spatial spread is 0.7–1 µm in cone outer segments, independently of their dimensions.

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