Simulation Analysis of Phototransduction Systems in Rods and Cones

Abstract

Retinal photoreceptor cells, rods and cones, are the key players in visual system, which convert photons of light into chemical and electrical signals. When light stimulate visual pigments (VPs) on membranous disks of photoreceptors, heterotrimeric G-proteins, transducins (Trs), are activated. Stimulated VPs are simultaneously desensitized through phosphorylation and inactivation processes. GTP-bound α subunits of the Trs subsequently activate phosphodiesterases (PDEs), which in turn, hydrolyzes cGMP. Decreasing in [cGMP]i deactivates the CNG channels and subsequently hyperpolarizes the photoreceptor, preventing the release of neurotransmitters. Time courses of light intensity-dependent photoresponses; changes in concentrations of phosphorylated VPs and activated Trs/PDEs, as well as CNG currents, both in rods and cones from carps were reported from Kawamura's group. Although the chemical processes through the visual transduction cascades in rods and cones are similar, their light senilities and temporal resolutions of the flash responses are quite different. These differences are attributed to distinct reaction rates throughout the visual phototransduction systems in these photoreceptor cells, however, have not been systematically investigated since none of the former models could reconstruct quantitative changes in molecular reactions during photoresponses. On the basis of the Hamer model, here we developed a detailed mathematical model of visual signal transduction system in order to quantitatively investigate how photoresponses are divergently regulated in rods and cones. The current models successfully reconstructed time courses of light intensity-, ATP- and GTP-dependent changes in concentrations of phosphorylated VPs and activated Trs/PDEs, as well as CNG currents in rods and cones reported by Kawamura's group. This study revealed that the assumption of the inactive state of VPs (MIIi) and RGS9-mediated inactivation of Trs in vivo are indispensable to simulate the CNG currents, which temporal resolutions are significantly higher than that for the changes in PDE activities in vitro.