Mathematical Analysis of Electrical Responses in Photoreceptor Cells Reveals Distinct Chemical Control of Visual Signal Transduction in Rods and Cones.

Abstract Retinal photoreceptor cells, rods and cones, convert photons of light into chemical and electrical signals as the first step of the visual transduction cascade. Although the chemical processes in the phototransduction system are very similar to each other in these photoreceptors, the light sensitivity and time resolution of the photoresponse in rods are functionally different than those in the photoresponses of cones. To systematically investigate how photoresponses are divergently regulated in rods and cones, we have developed a detailed mathematical model on the basis of the Hamer model. The current model successfully reconstructed light intensity-, ATP- and GTP-dependent changes in concentrations of phosphorylated visual pigments (VPs), activated transducins (Tr*s) and phosphodiesterases (PDEs), as well as cyclic nucleotide-gated currents (ICNG) in rods and cones. In comparison to rods, the lower light sensitivity of cones was attributed not only to the lower affinity of activated VPs for Trs but also to the faster desensitization of the VPs. The assumption of an intermediate inactive state, MIIi, in the thermal decay of activated VPs was pivotal for inducing faster inactivation of VPs. In addition to the faster inactivation of VPs, calculating a faster rate of RGS9 intervention for PDE-induced Tr* inactivation in cones was indispensable for simulating the electrical waveforms of the light intensity-dependent ICNG at higher temporal resolution in experimental systems in vivo.