Most vertebrate eyes have rod and cone photoreceptors, which use a signal transduction pathway consisting of many biological processes to transform light into an electrical response.r We dissect and quantify the contribution of each of these processes to the photoreceptor light response by using a novel method of analysis that provides an analytical solution for the entire time course of the dim-flash light response.r We find that the shape of the light response is exclusively controlled by deactivation parameters.Activation parameters scale this shape and alter the response amplitude.r We show that the rising phase of the response depends on Ca 2+ feedback, and we identify the deactivation parameters that control the recovery phase of the response.r We devise new methods to extract values for deactivation and activation parameters from a separate analysis of response shape and response amplitude.

Rod and cone photoreceptors in vertebrate eyes are fundamental sensory neurons underlying vision. They use a sophisticated signal transduction pathway consisting of a series of biochemical processes to convert the absorption of light into an electrical response. Several of these processes are modulated by feedback mechanisms that depend on the intracellular Ca2+ concentration. In this work we use a representative phototransduction model with fast buffering to study how the Ca2+ dynamics affects the light response of mouse rod and cone photoreceptors. We obtain analytic solutions for dim-light stimulation that reveal how the dynamics of the Ca2+ concentration and the electrical current are correlated. We show how modifying the Ca2+ dynamics via buffering affects amplitude and waveform of flash and step responses. We infer that under normal physiological conditions the change in the Ca2+ concentration is proportional to the current. We show that damped oscillations appear if the Ca2+ dynamics becomes slowed down and delayed with respect to the current, e.g. through the application of buffers. We find that oscillations do not require the presence of slow buffers. We show that the phase space of the dim-light response is controlled by the ratio between the effective rate μca that controls the Ca2+ dynamics, and the dark turnover rate of cyclic GMP βd. Finally, we investigate how the light response is affected by modifying the extracellular Ca2+ concentration. In summary, we provide a comprehensive analysis that reveals how the Ca2+ dynamics affects the dim-light response in rods and cones.SignificanceThe signal transduction pathway of vertebrate rod and cone photoreceptors transforms light into an electrical response. It is regulated by several feedback processes that depend on the intracellular Ca2+ concentration. Despite of the importance of this feedback for the photoreceptor functioning, it is not well studied how modifying the Ca2+ dynamics affects the light response, for example by adding buffers. Here we derive analytic results for dim-light stimulations that provide insight into how the Ca2+ dynamics and the electrical current response are correlated. Our analysis can be used to infer properties of the Ca2+ dynamics from the observed current response, and provides insight if direct measurements of the Ca2+ dynamics in the small outer segment of a photoreceptors are not available.