The rod pigment, rhodopsin, shows spontaneous isomerization activity. This quantal noise produces a dark light of ∼0.01 photons s−1 rod−1 in human, setting the threshold for rod vision. The spontaneous isomerization activity of human cone pigments has long remained a mystery because the effect of a single isomerized pigment molecule in cones, unlike that in rods, is small and beyond measurement. We have now overcome this problem by expressing human red cone pigment transgenically in mouse rods in order to exploit their large single-photon response, especially after genetic removal of a key negative-feedback regulation. Extrapolating the measured quantal noise of transgenic cone pigment to native human red cones, we obtained a dark rate of ∼10 false events s−1 cone−1, almost 103-fold lower than the overall dark transduction noise previously reported in primate cones. Our measurements provide a rationale for why mammalian red, green and blue cones have comparable sensitivities, unlike their amphibian counterparts.
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We thank J. Lai for help in generating the transgene construct, Y. Liang, L. Ding, and Y. Wang for mouse genotyping, J. Chen (University of Southern California School of Medicine) for the Gcaps−/− and Sag−/− mice and J. Lem (Tufts University School of Medicine) for the Rho−/− mice, as well as J. Nathans (Johns Hopkins University School of Medicine) and R. Molday (University of British Columbia) for their gifts of antibodies. We are indebted to P. Ala-Laurila, D. Baylor, and J. Schnapf for discussions. This work was supported by grant EY 06837 from the US National Eye Institute to K.-W.Y.
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Proceedings of the National Academy of Sciences (2019)
The Journal of General Physiology (2019)
Journal of the Optical Society of America A (2019)