Properties of Cytoplasmic Transmitters of Excitation in Vertebrate Rods and Evaluation of Candidate Intermediary Transmitters

  • E. N. PughJr.
  • W. H. Cobbs
Conference paper
Part of the Dahlem Workshop Reports book series (DAHLEM, volume 34)


A cytoplasmically diffusing substance or transmitter must carry the message of excitation from the vertebrate rod disk membrane to the rod plasma membrane, there effecting a decrease in the light-sensitive membrane current. A number of general properties of the transmitter molecule that communicates excitation to the rod plasma membrane either can be deduced from or are strongly constrained by facts of rod physiology. Here we analyze seven general properties of an excitational transmitter: a) transmitter sign (positive or negative concentration change induced by light); b) multi-order sequence of events in production/ destruction; c) numerical gain in production; d) restricted longitudinal diffusion along the outer segment; e) buffering effects on gain and diffusion coefficient; f) limited transmitter lifetime; and g) linearity of transmitter production/reduction with light intensity. Although only cGMP and calcium have been hypothesized to be the molecule communicating excitation to the plasma membrane, other substances have been hypothesized to serve as intermediary transmitters in excitation. We examine the following five intermediary transmitter candidates in the light of the seven general properties: (i) G-protein; (ii) protons; (iii) 5′GMP; (iv) cGMP-dependent protein kinase; and (v) inositol-1, 4, 5-trisphosphate.


Outer Segment Disk Membrane Longitudinal Diffusion Transmitter Candidate cGMP Hydrolysis 
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  1. (1).
    Atkins, P.W. 1978. Physical Chemistry. San Francisco: Freeman.Google Scholar
  2. (2).
    Bader, C.R.; MacLeish, P.R.; and Schwartz, E.A. 1979. A voltageclamp study of the light response in solitary rods of the tiger salamander. J. Physiol. 296: 1–26.PubMedGoogle Scholar
  3. (3).
    Baehr, W.; Morita, E.A.; Swanson, R.J.; and Applebury, M.L. 1982. Characterization of bovine rod outer segment G-protein. J. Biol. Chem. 257: 6452–6460.PubMedGoogle Scholar
  4. (4).
    Baylor, D.A.; Hodgkin, A.L.; and Lamb, T.D. 1974. The electrical response of turtle cones to flashes and steps of light. J. Physiol. 242: 685–727.PubMedGoogle Scholar
  5. (5).
    Baylor, D.A.; Lamb, T.D.; and Yau, K.-W. 1979a. The membrane current of single rod outer segments. J. Physiol. 288: 589–611.PubMedGoogle Scholar
  6. (6).
    Baylor, D.A.; Lamb, T.D.; and Yau, K.-W. 1979b. Responses of retinal rods to single photons. J. Physiol. 288: 613–634.PubMedGoogle Scholar
  7. (7).
    Baylor, D.A.; Matthews, G.; and Yau, K.-W. 1980. Two components of electrical dark noise in toad retinal rod outer segments. J. Physiol. 309: 591–621.PubMedGoogle Scholar
  8. (8).
    Baylor, D.A.; Matthews, G.; and Yau, K.-W. 1983. Temperature effects on the membrane current of retinal rods of the toad. J. Physiol. 337: 723–734.PubMedGoogle Scholar
  9. (9).
    Baylor, D.A., and Nunn, B.J. 1985. Electrical properties of the light-sensitive conductance of salamander rods. J. Physiol., in press.Google Scholar
  10. (10).
    Bennett, N. 1982. Light-induced interactions between rhodopsin and the GTP-binding protein: relation with phosphodiesterase activation. Eur. J. Biochem. 123: 133–139.PubMedCrossRefGoogle Scholar
  11. (11).
    Berger, S.J.; DeVries, G.W.; Carter, J.G.; Schulz, D.W.; Passonneau, P.N.; Lowry, O.H.; and Ferrendelli, J.A. 1980. The distribution of the components of the cGMP cycle in retina. J. Biol. Chem. 255: 3128–3133.PubMedGoogle Scholar
  12. (12).
    Berridge, M.J. 1983. Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem. J. 212: 849–858.PubMedGoogle Scholar
  13. (13).
    Bodoia, R.D., and Detwiler, P.B. 1984. Patch-clamp study of the light response of isolated frog retinal rods. Biophys. J. 45: 337a.CrossRefGoogle Scholar
  14. (14).
    Bownds, M.D. 1981. Biochemical pathways regulating transduction in frog photoreceptor membranes. Curr. Top. Membr. Trans. 15: 203–214.Google Scholar
  15. (15).
    Brown, J.E.; Rubin, L.J.; Ghalayini, A.J.; Taver, A.P.; Irvine, R.F.; Berridge, M.J.; and Anderson, R.E. 1984. Myo-inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors. Nature 311: 160–162.PubMedCrossRefGoogle Scholar
  16. (16).
    Chabre, M.; Vuong, M.; and Stryer, L. 1982. Anisotropy of the infrared light-scattering changes induced by illumination of oriented retinal rod outer segments. Biophys. J. 37: 247a.Google Scholar
  17. (17).
    Clack, J.W.; Oakley, B. II.; and Stein, P.J. 1983. Injection of GTP-binding protein or cGMP phosphodiesterase hyperpolarizes retinal rods. Nature 305: 50–52.PubMedCrossRefGoogle Scholar
  18. (18).
    Cohen, A.I. 1968. New evidence supporting the linkage to extracellular space of outer segment saccules of trog cones but not rods. J. Cell. Biol. 37: 424–444.PubMedCrossRefGoogle Scholar
  19. (19).
    Corson, D.W., and Fein, A. 1983a. Chemical excitation of Limulus photoreceptors. I. Phosphatase inhibitors induce discrete wave production in the dark. J. Gen. Physiol. 82: 639–657.Google Scholar
  20. (20).
    Corson, D.W., and Fein, A, 1983b. Chemical excitation of Limulus photoreceptors. II. Vanadate, GTP-g-S and fluoride prolong excitation evoked by dim flashes of light. J. Gen. Physiol. 82: 659–677.Google Scholar
  21. (21).
    Cote, R.H.; Biernbaum, M.S.; Nicol, G.D.; and Bownds, M.D. 1984. Light-induced decreases in cGMP concentration precede changes in membrane permeability in frog rod photoreceptors. J. Biol. Chem. 259: 9635–9641.PubMedGoogle Scholar
  22. (22).
    Crank, J. 1975. The Mathematics of Diffusion, 2nd ed. London: Oxford Press.Google Scholar
  23. (23).
    Dearry, A. 1981. Rod outer segment phosphodiesterase: a study on light-induced activity in whole retina using bromcresol purple. Ph.D. Dissertation, University of Pennsylvania.Google Scholar
  24. (24).
    DeFelice, L.J. 1981. Introduction to Membrane Noise. New York: Plenum.CrossRefGoogle Scholar
  25. (25).
    Detwiler, P.B.; Conner, J.D.; and Bodoia, R.D. 1982. Gigaseal patch clamp recordings from outer segments of intact retinal rods. Nature 300: 59–61.PubMedCrossRefGoogle Scholar
  26. (26).
    Dratz, E.A.; Miljanich, G.P.; Nemes, P.P.; Gaw, J.E.; and Schwartz, S. 1979. The structure of rhodopsin and its disposition in the rod outer segment disk membrane. Photochem. Photobiol. 29: 661–670.PubMedCrossRefGoogle Scholar
  27. (27).
    Eigen, M. 1973. Diffusion control in biochemical reactions. In Quantum Statistical Mechanics in the Natural Sciences, eds. S.L. Mintz and S.M. Widmayer, pp. 37–61. New York: Plenum.Google Scholar
  28. (28).
    Emrich, H. 1971. Optical measurements of the rapid pH change in the visual process during the metarhodopsin I-II reaction. Z. Naturforsch. 266: 352–356.Google Scholar
  29. (29).
    Farber, D.B.; Brown, B.M.; and Lolley, R.N. 1978. Cyclic GMP: proposed role in visual function. Vision Res. 18: 497–500.PubMedCrossRefGoogle Scholar
  30. (30).
    Fein, A.; Payne, R.; Corson, D.W.; Berridge, M.J.; and Irvine, R.F. 1984. Photoreceptor excitation and adaptation by inositol-1, 4, 5-trisphosphate. Nature 311: 157–160.PubMedCrossRefGoogle Scholar
  31. (31).
    Fliesler, S.J., and Anderson, R.E. 1983. Chemistry and metabolism of lipids in the vertebrate retina. Prog. Lipid Res. 22: 79–131.PubMedCrossRefGoogle Scholar
  32. (32).
    Fung, B.K.; Hurley, J.B.; and Stryer, L. 1981. Flow of information in the light-triggered cyclic nucleotide cascade of vision. Proc. Natl. Acad. Sci. USA 78: 152–156.PubMedCrossRefGoogle Scholar
  33. (33).
    Fung, B.K., and Stryer, L. 1980. Photolyzed rhodopsin catalyzes the exchange of GTP for bound GDP in retinal rod outer segments. Proc. Natl. Acad. Sci. USA 77: 2500–2504.CrossRefGoogle Scholar
  34. (34).
    Gedney, C., and Ostroy, S.E. 1978. Hydrogen ion effects of the vertebrate photoreceptor: the pK’s of ionizable groups affecting cell permeability. Arch. Biochem. Biophys. 188: 105–113.PubMedCrossRefGoogle Scholar
  35. (35).
    George, J.S., and Hagins, W.A.H. 1983. Control of Ca2+ in rod outer segment disks by light and cGMP. Nature 303: 344–348.PubMedCrossRefGoogle Scholar
  36. (36).
    Godchaux, W. III., and Zimmerman, W.F. 1979. Membrane-dependent guanine nucleotide binding and GTP-ase activities of soluble protein from bovine rod cell outer segments. J. Biol. Chem. 254: 7874–7884.PubMedGoogle Scholar
  37. (37).
    Goldberg, N.D.; Ames, A. III.; Gander, J.E.; and Walseth, T.F. 1983. Magnitude of increase in retinal cGMP metabolic flux determined byGoogle Scholar
  38. 18.
    O incorporation into nucleotide a-phosphoryls corresponds with intensity of photic stimulation. J. Biol. Chem. 258: 9213-9219.Google Scholar
  39. (38).
    Gomperts, B.D. 1983. Involvement of guanine nucleotide-binding protein in the gating of Ca2+ by receptors. Nature 306: 64–66.PubMedCrossRefGoogle Scholar
  40. (39).
    Govardovskii, V.I., and Berman, A.L. 1981. Light-induced changes of cGMP content in frog retinal rod outer segments measured with rapid freezing and microdissection. Biophys. Struct. Mech. 7: 125–130.PubMedCrossRefGoogle Scholar
  41. (40).
    Greengard, P. 1978. Phosphorylated proteins as physiological effectors. Science 199: 146–152.PubMedCrossRefGoogle Scholar
  42. (41).
    Hagins, W.A.; Penn, R.D.; and Yoshikami, S. 1970. Dark current and photocurrent in retinal rods. Biophys. J. 10: 380–412.PubMedCrossRefGoogle Scholar
  43. (42).
    Hagins, W.A., and Yoshikami, S. 1977. Intracellular transmission of visual excitation in photoreceptors: electrical effects of chelating agents introduced into rods by vesicle fusion. In Vertebrate Photoreception, eds. H.B. Barlow and P. Fatt, pp. 97–139. New York: Academic.Google Scholar
  44. (43).
    Kilbride, P., and Ebrey, T.G. 1979. Light-initiated changes of cGMP levels in the frog retina measured with quick-freezing techniques. J. Gen. Physiol. 74: 415–426.PubMedCrossRefGoogle Scholar
  45. (44).
    Kühn, H. 1980. Light-and GTP-regulated interaction of GTP-ase and other proteins with bovine photoreceptor membranes. Nature 283: 587–589.PubMedCrossRefGoogle Scholar
  46. (45).
    Kühn, H. 1981. Interactions of rod cell proteins with the disk membranes: influence of light, ionic strength and nucleotides. Curr. Top. Membr. Trans. 15: 172–199.Google Scholar
  47. (46).
    Kühn, H.; Bennett, N.; Michel-Villaz, M.; and Chabre, M. 1981. Interactions between photoexcited rhodopsin and GTP-binding protein: kinetic and stoichiometric analyses from light-scattering changes. Proc. Natl. Acad. Sci. USA 78: 6873–6877.PubMedCrossRefGoogle Scholar
  48. (47).
    Lamb, T.D. 1984. Effects of temperature on toad rod photocurrents. J. Physiol. 346: 557–578.PubMedGoogle Scholar
  49. (48).
    Lamb, T.D. 1984. Electrical responses of photoreceptors. In Recent Advances in Physiology, ed. P.F. Baker. London: Churchill Livingstone.Google Scholar
  50. (49).
    Lamb, T.D.; McNaughton, P.A.; and Yau, K.-W. 1981. Spatial spread of activation and background desensitization in toad rod outer segments. J. Physiol. 319: 463–496.PubMedGoogle Scholar
  51. (50).
    Lewis, J.W.; Miller, J.L.; Mendel-Hartvig, J.; Schaechter, L.E.; Kliger, D.S.; and Dratz, E.A. Sensitive light-scattering probe of enzymatic processes in retinal rod photoreceptor membranes. Proc. Natl. Acad. Sci. USA 81: 743–747.Google Scholar
  52. (51).
    Liebman, P.A.; Mueller, P.; and Pugh, E.N., Jr. 1984. Protons suppress the dark current of frog retinal rods. J. Physiol. 347: 85–110.PubMedGoogle Scholar
  53. (52).
    Liebman, P.A., and Pugh, E.N., Jr. 1980. ATP mediates rapid reversal of cGMP phosphodiesterase activation in visual receptor membranes. Nature 287: 734–736.PubMedCrossRefGoogle Scholar
  54. (53).
    Liebman, P.A., and Pugh, E.N., Jr. 1981. Control of rod disk membrane phosphodiesterase and a model for visual transduction. Curr. Top. Membr. Trans. 15: 157–169.Google Scholar
  55. (54).
    Liebman, P.A., and Pugh, E.N., Jr. 1982. Gain, speed and sensitivity of GTP-binding vs. PDE activation in visual excitation. Vision Res. 22: 1475–1480.Google Scholar
  56. (55).
    Liebman, P.A.; Weiner, H.L.; and Dryzmala, R.D. 1982. Lateral diffusion of visual pigment in rod disk membranes. Meth. Enzym. 81: 660–668.PubMedCrossRefGoogle Scholar
  57. (56).
    Lipton, S.A.; Rasmussen, H.; and Dowling, J.E. 1977. Electrical and adaptive properties of rod photoreceptors in Bufo marinus. II. Effects of cyclic nucleotides and prostaglandins. J. Gen. Physiol. 70: 771–791.PubMedCrossRefGoogle Scholar
  58. (57).
    MacLeish, P.R.; Schwartz, E.A.; and Tachibana, M. 1984. Control of the generator current in solitary rods of the Ambystoma tigrinum retina. J. Physiol. 348: 645–664.PubMedGoogle Scholar
  59. (58).
    McLaughlin, S. 1977. Electrostatic potentials at membrane-solution interfaces. Curr. Top. Membr. Trans. 9: 71–144.CrossRefGoogle Scholar
  60. (59).
    McLaughlin, S., and Brown, J. 1981. Diffusion of calcium ions in retinal rods. J. Gen. Physiol. 77: 475–487.PubMedCrossRefGoogle Scholar
  61. (60).
    Miljanivich, G.P.; Nemes, P.P.; White, D.L.; and Dratz, E.A. 1981. The asymmetric distribution of phosphotidylethanolamine, phosphatidylserine and fatty acids of the bovine retinal rod outer segment disk membrane. J. Membr. Biol. 60: 249–255.CrossRefGoogle Scholar
  62. (61).
    Miller, W.H., and Nicol, G.D. 1979. Evidence that cGMP regulates membrane potential in rod photoreceptors. Nature 280: 64–66.CrossRefGoogle Scholar
  63. (62).
    Mueller, P., and Pugh, E.N., Jr. 1983. Protons block the dark current of isolated retinal rods. Proc. Natl. Acad. Sci. USA 80: 1892–1896.PubMedCrossRefGoogle Scholar
  64. (63).
    Nicol, G.D., and Miller, W.H. 1978. Cyclic GMP injected into retinal rod outer segments increases latency and amplitude of response to illumination. Proc. Natl. Acad. Sci. USA 75: 5217–5220.PubMedCrossRefGoogle Scholar
  65. (64).
    Nishizuka, Y. 1984. Turnover of inositol phospholipids and signal transduction. Science 225: 1365–1370.PubMedCrossRefGoogle Scholar
  66. (65).
    Nunn, B.J., and Baylor, D.A. 1982. Visual transduction in retinal rods of the monkey Macaca fascicularis. Nature 299: 726–728.PubMedCrossRefGoogle Scholar
  67. (66).
    Olive, J. 1980. The structural organization of mammalian retinal disk membrane. Int. Rev. Cytol. 64: 107–169.PubMedCrossRefGoogle Scholar
  68. (67).
    Penn, R.D., and Hagins, W.A. 1972. Kinetics of the photocurrent of retinal rods. Biophys. J. 12: 1073–1094.PubMedCrossRefGoogle Scholar
  69. (68).
    Pfister, C.; Kühn, H.; and Chabre, M. 1983. Interaction between photoexcited rhodopsin and peripheral enzymes: influence of the postmetarhodopsin II decay and phosphorylation rate of rhodopsin. Eur. J. Biochem. 136: 489–499.PubMedCrossRefGoogle Scholar
  70. (69).
    Pinto, L.H., and Ostroy, S.E. 1978. Ionizable groups and conductances of the rod photoreceptor membrane. J. Gen. Physiol. 71: 329–345.PubMedCrossRefGoogle Scholar
  71. (70).
    Polans, A.S.; Hermolin, J.; and Bownds, M.D. 1979. Light-induced dephosphorylation of two proteins in frog rod outer segments. J. Gen. Physiol. 74: 595–613.PubMedCrossRefGoogle Scholar
  72. (71).
    Pugh, E.N., Jr., and Liebman, P.A. 1980. Delays and sensitivity support lateral diffusion hypothesis of multiple PDE activation by single rhodopsin. Fed. Proc. 39: 1815a.Google Scholar
  73. (72).
    Robinson, W.E., and Hagins, W.A. 1979. GTP hydrolysis in intact rod outer segments and the transmitter cycle in visual excitation. Nature 280: 398–400.PubMedCrossRefGoogle Scholar
  74. (73).
    Riippel, H., and Hagins, W.A. 1973. Spatial origin of the fast photovoltage in retinal rods. In Biochemistry and Physiology of Visual Pigments, ed. H. Langer, pp. 257–262. New York: Springer.Google Scholar
  75. (74).
    Schmidt, S.Y. 1983. Light enhances the turnover of phosphatidylinositol in rat retinas. J. Neurochem. 40: 1630–1638.PubMedCrossRefGoogle Scholar
  76. (75).
    Schnapf, J. 1983. Dependence of the single photon response on longitudinal position of absorption in toad rod outer segments. J. Physiol. 343: 147–159.PubMedGoogle Scholar
  77. (76).
    Sitaramayya, A., and Liebman, P.A. 1983a. Mechanism of ATP-dependent quench of phosphodiesterase activation in rod disk membranes. J. Biol. Chem. 258: 1205–1209.PubMedGoogle Scholar
  78. (77).
    Sitaramayya, A., and Liebman, P.A. 1983b. Phosphorylation of rhodopsin and quenching of cGMP phosphodiesterase activation by ATP at weak bleaches. J. Biol. Chem. 258: 12106–12109.PubMedGoogle Scholar
  79. (78).
    Streb, H.; Irvine, R.F.; Berridge, M.J.; and Schulz, I. 1983. Release of Ca2+ from a non-mitochondrial store in pancreatic acinar cells by inositol-1, 4, 5-trisphosphate. Nature 306: 67–69.PubMedCrossRefGoogle Scholar
  80. (79).
    Szabo, A.; Schulten, K.; and Schulten, Z. 1980. First passage time approach to diffusion-controlled reactions. J. Chem. Phys. 72: 4350–4357.CrossRefGoogle Scholar
  81. (80).
    Wormington, C.M., and Cone, R.A. 1978. Ionic blockage of the light-regulated sodium channels in isolated rod outer segments. J. Gen. Physiol. 71: 657–681.PubMedCrossRefGoogle Scholar
  82. (81).
    Yee, R., and Liebman, P.A. 1978. Light-activated phosphodiesterase of the rod outer segment: kinetic parameters of activation and deactivation. J. Biol. Chem. 253: 8902–8909.PubMedGoogle Scholar
  83. (82).
    Yoshikami, S., and Hagins, W.A. 1984. Phototransduction in rods does not require a change in cytoplasmic pH. Biophys. J. 45: 339a.Google Scholar
  84. (83).
    Yoshikami, S.; Robinson, W.E.; and Hagins, W.A. 1974. Topology of the outer segment membranes of retinal rods and cones revealed by a fluorescent probe. Science 185: 1176–1179.PubMedCrossRefGoogle Scholar

Copyright information

© Dr. S. Bernhard, Dahlem Konferenzen, Berlin 1986

Authors and Affiliations

  • E. N. PughJr.
    • 1
  • W. H. Cobbs
    • 2
  1. 1.Dept. of PsychologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Dept. of NeurologyUniversity of Pennsylvania Medical SchoolPhiladelphiaUSA

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