Modeling of the phototransduction cascade in vertebrate rod photoreceptor

Abstract

The molecular mechanisms of phototransduction in the rod photoreceptor cell have been reasonably well established but have not been represented in the form of a system model. In this work, we formulated a basic system model structure by representing the major biochemical reactions in the phototransduction cascade as a seventh-order system of kinetic equations with the ERG a-wave as a measurable output. The model structure was tested for its usefulness in describing the ERG a-wave under different experimental conditions. Wild type, NOB1, and photoreceptor-damaged (by light or drug) mice were stimulated with two light patterns of three intensities. The model structure could very well describe the ERG a-waves for various subject-stimulus combinations tested. Estimated parameter values were applicable to new subjects if they were not expected to change. A variable model parameter could not only differentiate photoreceptor-damaged subjects from healthy ones but also indicated the level of damage. Longer-term simulation by the model showed expected photoreceptor responses for the termination and modulation phases. The model structure showed much promise as a basic form of representation for the phototransduction kinetics in rods.