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PB Detwiler, S Ramanathan, A Sengupta, BI Shraiman; Local Saturation of the Transduction Cascade and Reproducibility of the Single Photon Response . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1415.
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Purpose: To describe the conditions that limit the spatial spread of the activated transduction cascade (local saturation) and evaluate its influence on the reproducibility of the single photon response. Methods: This is a theoretical examination of the consequences of two facts: 1. Single photon activation of transducin (T) is local. 2. Spread of activated T and stimulation of phosphodiesterase (PDE) is limited by diffusion. Results: The first step in the transduction cascade is highly amplified; one Rh* activates many (100 - 1000) T. Hence, in the immediate vicinity of a single Rh* more T will be activated than available PDE, causing all the PDE in the close surround to be stimulated. The radius of the spot of fully activated PDE will increase with increasing Rh* lifetime until it reaches a limiting (saturating) size (rmax). This occurs when the rates of PDE activation and inactivation are equal. It can be shown that: rmax = [K1 / KH * (PDE)total * π]0.5 where K1 is rate of T activation, KH is rate of PDE* inactivation and (PDE)total is the density (#/µm2) of all the PDE. rmax forms in time tS = rmax2 / DT, where DT is the diffusion coefficient for T (∼1 µm2/s). The exact values of the relevant variables are not well established, but published estimatess are consistent with rmax =∼1µm and tS =∼1s. Conclusion: A single Rh* molecule that lives longer than tS will cause local saturation. All the PDE molecules in area rmax2π on the disk membrabe will be excited and the resulting photoresponse will have a fixed (saturated) amplitude. This would reduce the variability of the single photon response by limiting the response generated by all Rh* molecules that remain active for time ≷ tS. This local saturation effect acting together with 2-3 step Rh* shutoff can account for the observed small trail-to-trail variation in the amplitude of the single photon response, i.e. the reproducibilty of the single photon response.
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