Hostname: page-component-74656f9884-8r8nv Total loading time: 0 Render date: 2026-11-10T07:13:02.072Z Has data issue: false hasContentIssue false
  • English
  • Français

Phototransduction: Modeling the primate cone flash response

Published online by Cambridge University Press:  02 June 2009

Russell D. Hamer  and
Christopher W. Tyler
Russell D. Hamer
Affiliation:
Smith-Kettlewell Eye Research Institute, San Francisco
Christopher W. Tyler
Affiliation:
Smith-Kettlewell Eye Research Institute, San Francisco
Get access Rights & Permissions [Opens in a new window]

Abstract

We have developed a new model of phototransduction that accounts for the dynamics of primate and human cone flash responses in both their linear and saturating range. The model incorporates many of the known elements of the phototransduction cascade in vertebrate photoreceptors. The input stage is a new analytic expression for the activation and inactivation of cGMP-phosphodiesterase (PDE). Although the Lamb and Pugh (1992) model (of a delayed ramp for the rising phase of the PDE* response in amphibian rods) provided a good fit for the first 2 log units of stimulus intensity without parameter adjustments, the remaining 4 log units of the data required nonlinear modifications of both delay and gain (slope). We show that this nonlinear behavior is a consequence of the delay approximation and develop a completely linear model to account for the rising phase of amphibian rod photocurrent responses over the full intensity range (~6 log units). We use the same dynamic model to account for primate cone responses by decreasing the time constants of PDE activation and introducing an enhanced inactivation process. This PDE* response activates a nonlinear calcium feedback stage that modulates guanylate cyclase synthesis of cyclic GMP. By adjustment of the throughput and feedback parameters, the full model successfully captures most of the features of the primate and human cone flash responses throughout their dynamic range. Our analysis suggests that initial processes in the transduction cascade may be qualitatively different from comparable processes in rods.

Keywords

Cone modelVisual transductionPhototransductionPhotoreceptorsSaturation

Information

Type
Research Articles
Information
Visual Neuroscience , Volume 12 , Issue 6 , November 1995 , pp. 1063 - 1082
Copyright
Copyright © Cambridge University Press 1995

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Ames, Adelbert III. (1994). Steady state feedback in mammalian phototransduction illustrated by a nomogram. Vision Research 34, 821–827.CrossRefGoogle ScholarPubMed
Applebury, M.L. & Chabre, M. (1986). Interaction of photo-activated rhodopsin with photoreceptors proteins: The cyclic CMP cascade. In The Molecular Mechanism of Photoreception, ed. Stieve, H., pp. 51–66, Dahlem Konferenzen, Berlin: Springer-Verlag.Google Scholar
Arshavsky, V.Y. & Bownds, M.D. (1992). Regulation of deactivation of photoreceptor G protein by its target enzyme and cGMP. Nature 357, 416–417.CrossRefGoogle Scholar
Baron, W.S. & Boynton, R.M. (1975). Response of primate cones to sinusoidally flickering homochromatic stimuli. Journal of Physiology 246, 311–331.CrossRefGoogle ScholarPubMed
Baylor, D.A. (1987). Photoreceptor signals and vision. Investigative Ophthalmology and Visual Science 28, 34–49.Google ScholarPubMed
Baylor, D.A., Hodgkin, A.L. & Lamb, T.D. (1974). The electrical response of turtle cones to flashes and steps of light. Journal of Physiology 242, 685–727.CrossRefGoogle ScholarPubMed
Baylor, D.A., Lamb, T.D. & Yau, K.-W. (1979). Responses of retinal rods to single photons. Journal of Physiology 288, 613–634.CrossRefGoogle ScholarPubMed
Baylor, D.A. & Nunn, B.J. (1986). Electrical properties of the light-sensitive conductance of rods of the salamander ambystoma tigrinum. Journal of Physiology 371, 115–145.CrossRefGoogle ScholarPubMed
Baylor, D.A., Nunn, B.J. & Schnapf, J.L. (1984). The photocurrent noise and spectral sensitivities of rods of the monkey Macaca fascicularis. Journal of Physiology 357, 575–607.CrossRefGoogle ScholarPubMed
Baylor, D.A., Nunn, B.J. & Schnapf, J.L. (1987). Spectral sensitivity of cones of the monkey Macaca fascicularis. Journal of Physiology 390; 145–160.CrossRefGoogle ScholarPubMed
Bennett, N., Michel-Villaz, M. & Kuhn, H. (1982). Light-induced interaction between rhodopsin and the GTP-binding protein: Meta-rhodopsin II is the major photoproduct involved. European Journal of Biochemistry 127, 97–103.CrossRefGoogle Scholar
Breton, M.E., Schueller, A.W., Lamb, T.D. & Puch, E.N. (1994). Analysis of ERG a-wave amplification and kinetics in terms of the G-protein cascade of phototransduction. Investigative Ophthalmology and Visual Science 35, 295–309.Google ScholarPubMed
Caretta, A. & Cavaggioni, A. (1983). Fast ionic flux activated by cyclic GMP in the membrane of cattle rod outer segments. European Journal of Biochemistry 132, 1–8.CrossRefGoogle ScholarPubMed
Cobbs, W.H. & Pugh, E.N. (1987). Kinetics and components of the flash photocurrent of isolated retinal rods of the larval salamander, Ambystoma tigrinum. Journal of Physiology 394, 529–572.CrossRefGoogle ScholarPubMed
DeVries, H. (1943). The quantum character of light and its bearing upon the threshold of vision, the differential sensitivity, and visual acuity of the eye. Physica 10, 553–564.CrossRefGoogle Scholar
Dawis, S.M., Graeff, R.M., Heyman, R.A., Walseth, T.F. & Goldberg, N.D. (1988). Regulation of cyclic GMP metabolism in toad photoreceptors. Journal of Biological Chemistry 263, 8771–8785.CrossRefGoogle ScholarPubMed
Fesenko, E.E., Kolesnikov, S.S. & Lyubarsky, A.L. (1985). Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. Nature 313, 310–313.CrossRefGoogle ScholarPubMed
Forti, S., Menini, A., Rispoli, G. & Torre, V. (1989). Kinetics of phototransduction in retinal rods of the newt Triturus Cristatus. Journal of Physiology 419, 265–295.CrossRefGoogle ScholarPubMed
Fung, B.B.-K. & Stryer, L. (1980). Photolyzed rhodopsin catalyzes the exchange of GTP for GDP in retinal rod outer segment membranes. Proceedings of the National Academy of Sciences of the U.S.A. 77, 2500–2504.CrossRefGoogle Scholar
Grzywacz, N.M. & Hillman, P. (1988). Biophysical evidence that light adaptation in Limulus photoreceptors is due to a negative feedback. Biophysical Journal 53, 337–348.CrossRefGoogle ScholarPubMed
McNaughton, P.A., Cervetto, L. & Nunn, B.J. (1986 b). Measurement of the intracellular free caleium concentration in salamander rods. Nature 322, 261–263.CrossRefGoogle ScholarPubMed
Menini, A., Rispoli, G. & Torre, V. (1988). The ionic selectivity of the light-sensitive current in isolated rods of the tiger salamander. Journal of Physiology 402, 279–300.CrossRefGoogle ScholarPubMed
Miller, J.L. & Korenbrot, J.I. (1994). Differences in calcium homeostasis between retinal rod and cone photoreceptors revealed by the effects of voltage on the cGMP-gated conductance in intact cells. Journal of General Physiology 104, 909–940.CrossRefGoogle ScholarPubMed
Miller, J.L., Picones, A. & Korenbrot, J.I. (1994). Differences in transduction between rod and cone photoreceptors: An exploration of the role of calcium homeostasis. Current Opinion in Neurobiology 4, 488–495.CrossRefGoogle ScholarPubMed
Nakatani, K. & Yau, K.-W. (1988). Calcium and llght adaptation in retinal rods and cones. Nature 334, 69–71.CrossRefGoogle ScholarPubMed
Nunn, B.J., Schnapf, J.L. & Baylor, D.A. (1984). Spectral sensitivity of single cones in the retina of Macaca fascicularis. Nature 309, 264–266.CrossRefGoogle ScholarPubMed
Pepe, I.M., Panfoli, I. & Cugnoli, C. (1986). Guanylate cyclase in rod outer segments of the toad retina. Effect of light and Ca2+. FEBS Letters 203, 73–76.CrossRefGoogle ScholarPubMed
Pugh, E.N. & Cobbs, W.H. (1986). Visual transduction in vertebrate rods and cones: A tale of two transmitters, calcium and cyclic GMP. Vision Research 26, 1613–1643.CrossRefGoogle ScholarPubMed
Pugh, E.N. & Altman, J. (1988). A role for calcium in adaptation. Nature 334, 16–17.CrossRefGoogle ScholarPubMed
Pugh, E.N. & Lamb, T.D. (1990). Cyclic GMP and calcium: The internal messengers of excitation and adaptation in vertebrate photoreceptors. Vision Research 30, 1923–1948.CrossRefGoogle ScholarPubMed
Pugh, E.N. & Lamb, T.D. (1993). Amplification and kinetics of the activation steps in phototransduction. Biochimica et Biophysica Acta 1141, 111–149.CrossRefGoogle ScholarPubMed
Ratto, G.M., Payne, R., Owen, W.G. & Tsien, R.Y. (1988). The concentration of cytosolic free calcium in vertebrate rod outer segments measured with fura-2. Journal of Neuroscience 8, 3240–3246.CrossRefGoogle ScholarPubMed
Rispoli, G., Sather, W.A. & Detwiler, P.B. (1988). Effect of triphosphate nucleotides in the response of detached rod outer segments in low external calcium. Biophysical Journal 53, 388a.Google Scholar
Schnapf, J.L., Kraft, T.W. & Baylor, D.A. (1987). Spectral sensitivity of human cone photoreceptors. Nature 325, 439–441.CrossRefGoogle ScholarPubMed
Schnapf, J.L., Kraft, T.W., Nunn, B.J. & Baylor, D.A. (1988). Spectral sensitivity of primate photoreceptors. Visual Neuroscience 1, 255–261.CrossRefGoogle ScholarPubMed
Schnapf, J.L., Nunn, B.J., Meister, M. & Baylor, D.A. (1990). Visual transduction in cones of the monkey macaca fascicularis. Journal of Physiology 427, 681–713.CrossRefGoogle ScholarPubMed
Sneyd, J. & Tranchina, D. (1989). Phototransduction in cones: An inverse problem in enzyme kinetics. Bulleiin of Mathematical Biology 51, 749–784.CrossRefGoogle ScholarPubMed
Stryer, L. (1988). Molecular basis of visual excitation. Cold Spring Harbor Symposia on Quantatative Biology 53, 283–294.CrossRefGoogle ScholarPubMed
Stryer, L. (1986). Cyclic GMP cascade of vision. Annual Review of Neuroscience 9, 87–119.CrossRefGoogle ScholarPubMed
Tamura, T., Nakatani, K. & Yau, K.-W. (1991). Calcium feedback and sensitivity regulation in primate rods. Journal of General Physiology 98, 95–130.CrossRefGoogle ScholarPubMed
Torre, V., Forti, S., Menini, A. & Campani, M. (1990). Model of phototransduction in retinal rods. In Cold Spring Harbor Symposium on Quantitative Biology, Vol. LV. The Brain, pp. 563–573. New York: Cold Spring Harbor Laboratory Press.Google Scholar
Torre, V., Matthews, H.R. & Lamb, T.D. (1986). Role of calcium in regulating the cyclic GMP cascade of phototransduction in retinal rods. Proceedings of the National Academy of Sciences of the U.S.A. 83, 7109–7113.CrossRefGoogle ScholarPubMed
Tranchina, D., Gordon, J. & Shapley, R. (1984). Retinal light adaptation-evidence for a feedback mechanism. Nature 310, 314–316.CrossRefGoogle ScholarPubMed
Tyler, C.W. & Hamer, R.D. (1990). Peripheral cone processing from single quanta to megaquantal flux levels. Investigative Ophthalmology & Visual Science 31 (Suppl.), 493.Google Scholar
Valeton, J.M. & van Norren, D. (1983). Light-adaptation of primate cones: An analysis based on extracellular data. Vision Research 23, 1539–1547.CrossRefGoogle ScholarPubMed
Vuong, T.M., Chabre, M. & Stryer, L. (1984). Millisecond activation of transducin in the cyclic nucleotide cascade of vision. Nature 311, 659–661.CrossRefGoogle ScholarPubMed
Yau, K.W. (1994). Phototransduction mechanism in retinal rods and cones. Investigative Ophthalmology and Visual Science 35, 9–32.Google ScholarPubMed
Yau, K.W., Haynes, L.W. & Nakatani, K. (1986). Roles of calcium and cyclic GMP in visual transduction. In Membrane Control of Cellular Activity, ed. Luttgau, H.-C., pp. 343–366. Stuttgart: Gustav Fischer.Google Scholar
Yau, K.W. & Nakatani, K. (1984). Electrogenic Na-Ca exchange in retinal rod outer segment. Nature 311, 661–663.CrossRefGoogle ScholarPubMed
Yau, K.W. & Nakatani, K. (1985 a). Light-induced reduction of cytoplasmic free calcium in retinal rod outer segment. Nature 313, 579–581.CrossRefGoogle ScholarPubMed
Yau, K.W. & Nakatani, K. (1985 b). Light-suppressible, cyclic-GMP-sensitive conductance in the plasma membrane of a truncated rod outer segment. Nature 317, 252–255.CrossRefGoogle ScholarPubMed
Zimmerman, A.L. & Baylor, D.A. (1986). Cyclic-GMP sensitive conductance of retinal rods consists of aqueous pores. Nature 321, 70–72.CrossRefGoogle ScholarPubMed