Detection of single photons by toad and mouse rods.
Amphibian and mammalian rods can both detect single photons of light even though they differ greatly in physical dimensions, mammalian rods being much smaller in diameter than amphibian rods. To understand the changes in physiology and biochemistry required by such large differences in outer segment geometry, we developed a computational approach, taking into account the spatial organization of the outer segment divided into compartments, together with molecular dynamics simulations of the signaling cascade. We generated simulations of the single-photon response together with intrinsic background fluctuations in toad and mouse rods. Combining this computational approach with electrophysiological data from mouse rods, we determined key biochemical parameters. On average around one phosphodiesterase (PDE) molecule is spontaneously active per mouse compartment, similar to the value for toad, which is unexpected due to the much smaller diameter in mouse. A larger number of spontaneously active PDEs decreases dark noise, thereby improving detection of single photons; it also increases cGMP turnover, which accelerates the decay of the light response. These constraints explain the higher PDE density in mammalian compared with amphibian rods that compensates for the much smaller diameter of mammalian disks. We further find that the rate of cGMP hydrolysis by light-activated PDE is diffusion limited, which is not the case for spontaneously activated PDE. As a consequence, in the small outer segment of a mouse rod only a few activated PDEs are sufficient to generate a signal that overcomes noise, which permits a shorter lifetime of activated rhodopsin and greater temporal resolution.
Institut de Biologie de l'École Normale Supérieure, Group of Computational Biology and Applied Mathematics, École Normale Supérieure, 75005 Paris, France.
Jürgen
J
Reingruber
Johan
J
Pahlberg
Michael L
ML
Woodruff
Alapakkam P
AP
Sampath
Gordon L
GL
Fain
David
D
Holcman
D000818:Animals; D001001:Anura; D048429:Cell Size; D006152:Cyclic GMP / Q000378:metabolism; D006868:Hydrolysis; D055537:Light Signal Transduction / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D017785:Photons; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology* / Q000502:physiology*; D013045:Species Specificity
D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP
analysis; mathematical modeling; phototransduction; stochastic