Hamer RD.

Retinal Computational Modeling, Smith-Kettlewell Eye Rsch Inst, 2318 Fillmore St, San Francisco, CA, 94115, USA

Purpose: Studies of vertebrate photoreceptor fuction often measure the T_sat fuction [i.e., the period of photocurrent saturation, T_sat vs. ln(I)], which is frequently (but not always!) linear over a significant I-range. The slope of the linear region is intrepreted as a measure of the time constant of the dominant (1^st order) recovery process (t_dom) in the cGMP cascade, usually assigned to either R^*- (t_R) or PDE^*-lifetime (t_PDE). However, empirical T_sat fuctions often deviate from linearity at low and/or high I, and some have no identifiable region of linearity (Hamer & Tyler, ARVO 96). The present study examines several mechanisms that, along with t_dom, can conjointly influence the overall form of the T_sat fuction. Methods: A phototransduction model was used to generate T_sat fuctions. The model included Ca⁺⁺ feedback onto t_R, a back reaction from inactivated to activated R^* (R^*fR), as well as explicit limitations on available R (R_tot), tranducin (T_tot), and PDE (PDE_tot). The parameters were optimized so as to reproduce the behavior of empirical photoreceptor responses. Results: (1) A T_sat fuction can have a ~linear range with a slope that may not reflect 1^st order inactivation of either R* or PDE*, but may reflect the combined influence of T, PDE dynamics & saturation, Ca⁺⁺ -dynamics, &/or the dynamics of R*<-R. (2) Acceleration of the T_sat fuction at high-I may reflect PDE saturation (Chen et al., 2000) or the influence of R^*fR, or both. (3) High-I acceleration is also influenced by the relative amounts of T_tot and PDE_tot. (4) Positively accelerating empirical T_sat fuctions can be explained by the combined influence of PDE-saturation, an R^*fR back-reaction, the value of t_dom, as well as the dynamics of changes in free Ca_i⁺⁺. (5) The effect of these factors on the form of the T_sat fuction differs depending on whether it is assumed that t_R or t_PDE is rate-limiting. Conclusions: The analyses have bearing on the interpretation of the T_sat function vis a vis phototransduction mechanisms. T_sat leaves must be read with caution.

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