Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Quantal noise from human red cone pigment

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mouse rods expressing transgenic human red cone pigment.
Figure 2: Responses and action spectrum of mouse rods expressing transgenic red cone pigment.
Figure 3: Estimate of percentage of red cone pigment in transgenic mouse rods.
Figure 4: Expression of human red cone pigment in Rho+/+Gcaps−/− background.
Figure 5: Measurement of spontaneous isomerization rate of red cone pigment.
Figure 6: Background adaptation of wild-type (Rho+/+) mouse rods.

Similar content being viewed by others

References

  1. Barlow, H.B. Increment thresholds at low intensities considered as signal/noise discriminations. J. Physiol. (Lond.) 136, 469–488 (1957).

    Article  CAS  Google Scholar 

  2. Barlow, H.B. Intrinsic noise of cones. In Visual Problems of Colour Vol. II, (ed. National Physical Laboratory, Teddington, England) 617–630 (Her Majesty's Stationery Office, London, 1958).

    Google Scholar 

  3. Donner, K. Noise and the absolute thresholds of cone and rod vision. Vision Res. 32, 853–866 (1992).

    Article  CAS  Google Scholar 

  4. Field, G.D., Sampath, A.P. & Rieke, F. Retinal processing near absolute threshold: from behaviour to mechanism. Annu. Rev. Physiol. 67, 491–514 (2005).

    Article  CAS  Google Scholar 

  5. Baylor, D.A., Matthews, G. & Yau, K.-W. Two components of electrical dark noise in toad rod outer segments. J. Physiol. (Lond.) 309, 591–621 (1980).

    Article  CAS  Google Scholar 

  6. Baylor, D.A., Nunn, B.J. & Schnapf, J.L. The photocurrent, noise & spectral sensitivity of rods of the monkey Macaca fascicularis. J. Physiol. (Lond.) 357, 575–607 (1984).

    Article  CAS  Google Scholar 

  7. Rieke, F. & Baylor, D.A. Molecular origin of continuous dark noise in rod photoreceptors. Biophys. J. 71, 2553–2572 (1996).

    Article  CAS  Google Scholar 

  8. Lamb, T.D. & Simon, E.J. Analysis of electrical noise in turtle cones. J. Physiol. (Lond.) 272, 435–468 (1977).

    Article  CAS  Google Scholar 

  9. Holcman, D. & Korenbrot, J.I. The limit of photoreceptor sensitivity: molecular mechanisms of dark noise in retinal cones. J. Gen. Physiol. 125, 641–660 (2005).

    Article  CAS  Google Scholar 

  10. Schneeweis, D.M. & Schnapf, J.L. Noise and light adaptation in rods of the macaque monkey. Vis. Neurosci. 17, 659–666 (2000).

    Article  CAS  Google Scholar 

  11. Schnapf, J.L., Nunn, B.J., Meister, M. & Baylor, D.A. Visual transduction in cones of the monkey Macaca fascicularis. J. Physiol. (Lond.) 427, 681–713 (1990).

    Article  CAS  Google Scholar 

  12. Schneeweis, D.M. & Schnapf, J.L. The photovoltage of macaque cone photoreceptors: adaptation, noise, and kinetics. J. Neurosci. 19, 1203–1216 (1999).

    Article  CAS  Google Scholar 

  13. Kefalov, V., Fu, Y., Marsh-Armstrong, N. & Yau, K.-W. Role of visual pigment properties in rod and cone phototransduction. Nature 425, 526–531 (2003).

    Article  CAS  Google Scholar 

  14. Lem, J. et al. Morphological, physiological, and biochemical changes in rhodopsin knockout mice. Proc. Natl. Acad. Sci. USA 96, 736–741 (1999).

    Article  CAS  Google Scholar 

  15. Xu, J. et al. Prolonged photoresponses in transgenic mouse rods lacking arrestin. Nature 389, 505–509 (1997).

    Article  CAS  Google Scholar 

  16. Okada, T. et al. Circular dichroism of metaiodopsin II and its binding to transducin: a comparative study between meta II intermediates of iodopsin and rhodopsin. Biochemistry 33, 4940–4946 (1994).

    Article  CAS  Google Scholar 

  17. Burns, M.E., Mendez, A., Chen, J. & Baylor, D.A. Dynamics of cyclic GMP synthesis in retinal rods. Neuron 36, 81–91 (2002).

    Article  CAS  Google Scholar 

  18. Mendez, A. et al. Role of guanylate cyclase-activating proteins (GCAPS) in setting the flash sensitivity of rod photoreceptors. Proc. Natl. Acad. Sci. USA 98, 9948–9953 (2001).

    Article  CAS  Google Scholar 

  19. Lem, J., Applebury, M.L., Falk, J.D., Flannery, J.G. & Simon, M.I. Tissue-specific and developmental regulation of rod opsin chimeric genes in transgenic mice. Neuron 6, 201–210 (1991).

    Article  CAS  Google Scholar 

  20. Luo, D.G. & Yau, K.-W. Rod sensitivity of neonatal mouse and rat. J. Gen. Physiol. 126, 263–269 (2005).

    Article  CAS  Google Scholar 

  21. Nakatani, K., Tamura, T. & Yau, K.-W. Light adaptation in retinal rods of the rabbit and two other nonprimate mammals. J. Gen. Physiol. 97, 413–435 (1991).

    Article  CAS  Google Scholar 

  22. Tamura, T., Nakatani, K. & Yau, K.-W. Calcium feedback and sensitivity regulation in primate rods. J. Gen. Physiol. 98, 95–130 (1991).

    Article  CAS  Google Scholar 

  23. Rieke, F. & Baylor, D.A. Origin and functional impact of dark noise in retinal cones. Neuron 26, 181–186 (2000).

    Article  CAS  Google Scholar 

  24. Shi, G., Yau, K.W., Chen, J. & Kefalov, V.J. Signaling properties of a short-wave cone visual pigment and its role in phototransduction. J. Neurosci. 27, 10084–10093 (2007).

    Article  CAS  Google Scholar 

  25. Sakurai, K. et al. Physiological properties of rod photoreceptor cells in green-sensitive cone pigment knock-in mice. J. Gen. Physiol. 130, 21–40 (2007).

    Article  Google Scholar 

  26. Sampath, A.P. & Baylor, D.A. Molecular mechanism of spontaneous pigment activation in retinal cones. Biophys. J. 83, 184–193 (2002).

    Article  CAS  Google Scholar 

  27. Bridges, C.D.B. Spectroscopic properties of porphyropsins. Vision Res. 7, 349–369 (1967).

    Article  CAS  Google Scholar 

  28. Donner, K., Firsov, M.L. & Govardovskii, V.I. The frequency of isomerization-like “dark” events in rhodopsin and porphyropsin rods of the bull-frog retina. J. Physiol. (Lond.) 428, 673–692 (1990).

    Article  CAS  Google Scholar 

  29. Ala-Laurila, P., Donner, K., Crouch, R.K. & Cornwall, M.C. Chromophore switch from 11-cis-dehydroretinal (A2) to 11-cis-retinal (A1) decreases dark noise in salamander red rods. J. Physiol. (Lond.) 585, 57–74 (2007).

    Article  CAS  Google Scholar 

  30. Kefalov, V.J. et al. Breaking the covalent bond – a pigment property that contributes to desensitization in cones. Neuron 46, 879–890 (2005).

    Article  CAS  Google Scholar 

  31. Dunn, F.A., Lankheet, M.J. & Rieke, F. Light adaptation in cone vision involves switching between receptor and post-receptor sites. Nature 449, 603–607 (2007).

    Article  CAS  Google Scholar 

  32. Tachibanaki, S., Shimauchi-Matsukawa, Y., Arinobu, D. & Kawamura, S. Molecular mechanisms characterizing cone photoresponses. Photochem. Photobiol. 83, 19–26 (2007).

    CAS  PubMed  Google Scholar 

  33. Nakatani, K. & Yau, K.W. Sodium-dependent calcium extrusion and sensitivity regulation in retinal cones of the salamander. J. Physiol. (Lond.) 409, 525–548 (1989).

    Article  CAS  Google Scholar 

  34. Miller, J.L., Picones, A. & Korenbrot, J.I. Differences in transduction between rod and cone photoreceptors: an exploration of the role of calcium homeostasis. Curr. Opin. Neurobiol. 4, 488–495 (1994).

    Article  CAS  Google Scholar 

  35. Ma, J. et al. A visual pigment expressed in both rod and cone photoreceptors. Neuron 32, 451–461 (2001).

    Article  CAS  Google Scholar 

  36. Perry, R.J. & McNaughton, P.A. Response properties of cones from the retina of the tiger salamander. J. Physiol. (Lond.) 433, 561–587 (1991).

    Article  CAS  Google Scholar 

  37. Wang, Y. et al. A locus control region adjacent to the human red and green visual pigment genes. Neuron 9, 429–440 (1992).

    Article  CAS  Google Scholar 

  38. MacKenzie, D., Arendt, A., Hargrave, P., McDowell, J.H. & Molday, R.S. Localization of binding sites for carboxyl terminal specific anti-rhodopsin monoclonal antibodies using synthetic peptides. Biochemistry 23, 6544–6549 (1984).

    Article  CAS  Google Scholar 

  39. Molday, L.L., Cook, N.J., Kaupp, U.B. & Molday, R.S. The cGMP-gated cation channel of bovine rod photoreceptor cells is associated with a 240-kDa protein exhibiting immunochemical cross-reactivity with spectrin. J. Biol. Chem. 265, 18690–18695 (1990).

    CAS  PubMed  Google Scholar 

  40. Harosi, F. Absorption spectra and linear dichroism of some amphibian photoreceptors. J. Gen. Physiol. 66, 357–382 (1975).

    Article  CAS  Google Scholar 

  41. Govardovskii, V.I., Fyhrquist, N., Reuter, T., Kuzmin, D.G. & Donner, K. In search of the visual pigment template. Vis. Neurosci. 17, 509–528 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to King-Wai Yau.

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1, Supplementary Note (PDF 258 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fu, Y., Kefalov, V., Luo, DG. et al. Quantal noise from human red cone pigment. Nat Neurosci 11, 565–571 (2008). https://doi.org/10.1038/nn.2110

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.2110

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing