Abstract
Purpose: :
We analyze the origin of the dark background noise in rod photoreceptors and identify several mechanisms required to achieve high rod fidelity for the single photon detection. We further investigate whether the background noise is regulated similarly in rods from different species.
Methods: :
Biophysical Modeling, Mathematical Analysis and Numerical Simulations.
Results: :
The molecular origin for the continuous dark noise in toad rods is spontaneous activations and deactivations of Phosphodiesterase (PDE). However, while the noise generated by rhodopsin activation after photon absorption is a topic of intense research, the dark background noise has been largely ignored in the past years. To investigate the properties of the dark noise, we developed a spatially resolved mathematical framework that allows performing simulations of a single photon response together with the background noise. The fluctuations in our current simulations are due to the variability of the PDE activation cascade after photon absorption, and due to stochastic spontaneous PDE activations occurring on the surface of the internal disk. By considering the compartmentalized inner structure of a rod outer segment (OS), we show that the catalytic activity of activated PDE depends on the OS radius, and furthermore, we find that the activity of a spontaneously activated PDE is much higher compared to previous estimations based on a well stirred outer segment. For toad rods, the simulations of the dark noise and the single photon response give results that are comparable to experimental measurements. A clear single photon response in mouse rods can be achieved using the following modifications in mouse compared to toad rods: - due to the smaller OS radius, the rate of spontaneous PDE activation has to be higher in mouse rods to generate a sufficient amount of spontaneously active PDE that reduces the variability in the amount of activated PDE - the catalytic activity of spontaneously activated PDE has to be downregulated in mouse compared to toad rods - the rate of PDE activation after a single photon absorption has to be higher in mouse rods in order to activate a sufficiently amount of PDE - because of a much reduced number of light activated PDE in mouse, the catalytic activity of light activated PDE has to be high, in contrast to the activity of spontaneously activated PDE, which has to be reduced.
Conclusions: :
Our results suggest that the catalytic activity of spontaneously activated PDE is much smaller compared to light activated PDE. Our results suggest that there should be specific mechanisms to control the activation and the catalytic activity of spontaneously activated PDE that are used to adapt spontaneous PDE activation to different species.
Keywords: photoreceptors • signal transduction • calcium