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Regulation of photoreceptor gap junction phosphorylation by adenosine in zebrafish retina

Published online by Cambridge University Press:  22 January 2014

HONGYAN LI ,
ALICE Z. CHUANG  and
JOHN O’BRIEN
HONGYAN LI
Affiliation:
The Richard S. Ruiz M.D., Department of Ophthalmology and Visual Science, The University of Texas Medical School, Houston, Texas
ALICE Z. CHUANG
Affiliation:
The Richard S. Ruiz M.D., Department of Ophthalmology and Visual Science, The University of Texas Medical School, Houston, Texas
JOHN O’BRIEN*
Affiliation:
The Richard S. Ruiz M.D., Department of Ophthalmology and Visual Science, The University of Texas Medical School, Houston, Texas Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas
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Abstract

Electrical coupling of photoreceptors through gap junctions suppresses voltage noise, routes rod signals into cone pathways, expands the dynamic range of rod photoreceptors in high scotopic and mesopic illumination, and improves detection of contrast and small stimuli. In essentially all vertebrates, connexin 35/36 (gene homologs Cx36 in mammals, Cx35 in other vertebrates) is the major gap junction protein observed in photoreceptors, mediating rod–cone, cone–cone, and possibly rod–rod communication. Photoreceptor coupling is dynamically controlled by the day/night cycle and light/dark adaptation, and is directly correlated with phosphorylation of Cx35/36 at two sites, serine110 and serine 276/293 (homologous sites in teleost fish and mammals, respectively). Activity of protein kinase A (PKA) plays a key role during this process. Previous studies have shown that activation of dopamine D4 receptors on photoreceptors inhibits adenylyl cyclase, down-regulates cAMP and PKA activity, and leads to photoreceptor uncoupling, imposing the daytime/light condition. In this study, we explored the role of adenosine, a nighttime signal with a high extracellular concentration at night and a low concentration in the day, in regulating photoreceptor coupling by examining photoreceptor Cx35 phosphorylation in zebrafish retina. Adenosine enhanced photoreceptor Cx35 phosphorylation in daytime, but with a complex dose–response curve. Selective pharmacological manipulations revealed that adenosine A2a receptors provide a potent positive drive to phosphorylate photoreceptor Cx35 under the influence of endogenous adenosine at night. A2a receptors can be activated in the daytime as well by micromolar exogenous adenosine. However, the higher affinity adenosine A1 receptors are also present and have an antagonistic though less potent effect. Thus, the nighttime/darkness signal adenosine provides a net positive drive on Cx35 phosphorylation at night, working in opposition to dopamine to regulate photoreceptor coupling via a push–pull mechanism. However, the lower concentration of adenosine present in the daytime actually reinforces the dopamine signal through action on the A1 receptor.

Keywords

AdenosineA2a receptorA1 receptorCx36Photoreceptor

Information

Type
Research Articles
Information
Visual Neuroscience , Volume 31 , Issue 3 , May 2014 , pp. 237 - 243
Copyright
Copyright © Cambridge University Press 2014 

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References

Attwell, D., Borges, S., Wu, S.M. & Wilson, M. (1987). Signal clipping by the rod output synapse. Nature 328, 522–524.Google Scholar
Blazynski, C. (1990). Discrete distributions of adenosine receptors in mammalian retina. Journal of Neurochemistry 54, 648–655.Google Scholar
Cohen, A.I. & Blazynski, C. (1990). Dopamine and its agonists reduce a light-sensitive pool of cyclic AMP in mouse photoreceptors. Visual Neuroscience 4, 43–52.CrossRefGoogle ScholarPubMed
Cohen, A.I., Todd, R.D., Harmon, S. & O’Malley, K.L. (1992). Photoreceptors of mouse retinas possess D4 receptors coupled to adenylate cyclase. Proceedings of the National Academy of Sciences of the United States of America 89, 12093–12097.CrossRefGoogle ScholarPubMed
Dearry, A. & Burnside, B. (1986). Dopaminergic regulation of cone retinomotor movement in isolated teleost retinas: I. Induction of cone contraction is mediated by D2 receptors. Journal of Neurochemistry 46, 1006–1021.Google Scholar
Fredholm, B.B., Arslan, G., Halldner, L., Kull, B., Schulte, G. & Wasserman, W. (2000). Structure and function of adenosine receptors and their genes. Naunyn Schmiedebergs Archives of Pharmacology 362, 364–374.Google Scholar
Fredholm, B.B., Ijzerman, A.P., Jacobson, K.A., Linden, J. & Muller, C.E. (2011). International union of basic and clinical pharmacology. LXXXI. Nomenclature and classification of adenosine receptors—an update. Pharmacological Reviews 63, 1–34.CrossRefGoogle ScholarPubMed
Hillman, D.W., Lin, D. & Burnside, B. (1995). Evidence for D4 receptor regulation of retinomotor movement in isolated teleost cone inner-outer segments. Journal of Neurochemistry 64, 1326–1335.Google Scholar
Hornstein, E.P., Verweij, J., Li, P.H. & Schnapf, J.L. (2005). Gap-junctional coupling and absolute sensitivity of photoreceptors in macaque retina. The Journal of Neuroscience 25, 11201–11209.Google Scholar
Jackson, C.R., Chaurasia, S.S., Zhou, H., Haque, R., Storm, D.R. & Iuvone, P.M. (2009). Essential roles of dopamine D4 receptors and the type 1 adenylyl cyclase in photic control of cyclic AMP in photoreceptor cells. Journal of Neurochemistry 109, 148–157.Google Scholar
Jacobson, K.A., Nikodijevic, O., Padgett, W.L., Gallo-Rodriguez, C., Maillard, M. & Daly, J.W. (1993). 8-(3-Chlorostyryl)caffeine (CSC) is a selective A2-adenosine antagonist in vitro and in vivo. FEBS Letters 323, 141–144.CrossRefGoogle ScholarPubMed
Katti, C., Butler, R. & Sekaran, S. (2013). Diurnal and circadian regulation of connexin 36 transcript and protein in the mammalian retina. Investigative Ophthalmology & Visual Science 54, 821–829.CrossRefGoogle ScholarPubMed
Klotz, K.N. (2000). Adenosine receptors and their ligands. Naunyn Schmiedebergs Archives of Pharmacology 362, 382–391.Google Scholar
Kothmann, W.W., Li, X., Burr, G.S. & O’Brien, J. (2007). Connexin 35/36 is phosphorylated at regulatory sites in the retina. Visual Neuroscience 24, 363–375.Google Scholar
Kothmann, W.W., Massey, S.C. & O’Brien, J. (2009). Dopamine-stimulated dephosphorylation of connexin 36 mediates AII amacrine cell uncoupling. The Journal of Neuroscience 29, 14903–14911.Google Scholar
Krizaj, D., Gabriel, R., Owen, W.G. & Witkovsky, P. (1998). Dopamine D2 receptor-mediated modulation of rod-cone coupling in the Xenopus retina. The Journal of Comparative Neurology 398, 529–538.Google Scholar
Kvanta, A., Seregard, S., Sejersen, S., Kull, B. & Fredholm, B.B. (1997). Localization of adenosine receptor messenger RNAs in the rat eye. Experimental Eye Research 65, 595–602.Google Scholar
Lamb, T.D. & Simon, E.J. (1976). The relation between intercellular coupling and electrical noise in turtle photoreceptors. The Journal of Physiology 263, 257–286.Google Scholar
Lebedev, D.S., Byzov, A.L. & Govardovskii, V.I. (1998). Photoreceptor coupling and boundary detection. Vision Research 38, 3161–3169.CrossRefGoogle ScholarPubMed
Li, H., Chuang, A.Z. & O’Brien, J. (2009). Photoreceptor coupling is controlled by connexin 35 phosphorylation in zebrafish retina. The Journal of Neuroscience 29, 15178–15186.CrossRefGoogle ScholarPubMed
Li, H. & O’Brien, J. (2012). Regulation of gap junctional coupling in photoreceptors. In Photoreceptors: Physiology, Types and Abnormalities, ed. Akutagawa, E. & Ozaki, K., Hauppauge, NY: Nova Science.Google Scholar
Li, H., Zhang, Z., Blackburn, M.R., Wang, S.W., Ribelayga, C.P. & O’Brien, J. (2013). Adenosine and dopamine receptors coregulate photoreceptor coupling via gap junction phosphorylation in mouse retina. The Journal of Neuroscience 33, 3135–3150.Google Scholar
Mangel, S.C., Baldridge, W.H., Weiler, R. & Dowling, J.E. (1994). Threshold and chromatic sensitivity changes in fish cone horizontal cells following prolonged darkness. Brain Research 659, 55–61.Google Scholar
Muller, C.E. & Jacobson, K.A. (2011). Xanthines as adenosine receptor antagonists. In Methylxanthines, Handbook of Experimental Pharmacology, Vol. 200, ed. Fredholm, B.B., pp. 151–200. Berlin, Heidelberg: Springer-Verlag.Google Scholar
Mundell, S.J. & Kelly, E. (1998). Evidence for co-expression and desensitization of A2a and A2b adenosine receptors in NG108-15 cells. Biochemical Pharmacology 55, 595–603.Google Scholar
Nelson, R. (1977). Cat cones have rod input: A comparison of the response properties of cones and horizontal cell bodies in the retina of the cat. The Journal of Comparative Neurology 172, 109–135.CrossRefGoogle ScholarPubMed
Nir, I., Harrison, J.M., Haque, R., Low, M.J., Grandy, D.K., Rubinstein, M. & Iuvone, P.M. (2002). Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors. The Journal of Neuroscience 22, 2063–2073.Google Scholar
Rey, H.L. & Burnside, B. (1999). Adenosine stimulates cone photoreceptor myoid elongation via an adenosine A2-like receptor. Journal of Neurochemistry 72, 2345–2355.Google Scholar
Ribelayga, C., Cao, Y. & Mangel, S.C. (2008). The circadian clock in the retina controls rod-cone coupling. Neuron 59, 790–801.CrossRefGoogle ScholarPubMed
Ribelayga, C. & Mangel, S.C. (2005). A circadian clock and light/dark adaptation differentially regulate adenosine in the mammalian retina. The Journal of Neuroscience 25, 215–222.CrossRefGoogle ScholarPubMed
Ribelayga, C., Wang, Y. & Mangel, S.C. (2002). Dopamine mediates circadian clock regulation of rod and cone input to fish retinal horizontal cells. The Journal of Physiology 544, 801–816.CrossRefGoogle ScholarPubMed
Stella, S.L. Jr., Bryson, E.J., Cadetti, L. & Thoreson, W.B. (2003). Endogenous adenosine reduces glutamatergic output from rods through activation of A2-like adenosine receptors. Journal of Neurophysiology 90, 165–174.Google Scholar
Stella, S.L. Jr., Bryson, E.J. & Thoreson, W.B. (2002). A2 adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina. Journal of Neurophysiology 87, 351–360.Google Scholar
Stella, S.L. Jr., Hu, W.D., Vila, A. & Brecha, N.C. (2007). Adenosine inhibits voltage-dependent Ca2+ influx in cone photoreceptor terminals of the tiger salamander retina. The Journal of Neuroscience Research 85, 1126–1137.Google Scholar
Stella, S.L. Jr. & Thoreson, W.B. (2000). Differential modulation of rod and cone calcium currents in tiger salamander retina by D2 dopamine receptors and cAMP. The European Journal of Neuroscience 12, 3537–3548.Google Scholar
Trumpler, J., Dedek, K., Schubert, T., de Sevilla Muller, L.P., Seeliger, M., Humphries, P., Biel, M. & Weiler, R. (2008). Rod and cone contributions to horizontal cell light responses in the mouse retina. The Journal of Neuroscience 28, 6818–6825.Google Scholar
Wang, Y. & Mangel, S.C. (1996). A circadian clock regulates rod and cone input to fish retinal cone horizontal cells. Proceedings of the National Academy Sciences of the United States of America 93, 4655–4660.Google Scholar
Witkovsky, P. (2004). Dopamine and retinal function. Documenta Ophthalmologica 108, 17–40.Google Scholar
Witkovsky, P., Stone, S. & Besharse, J.C. (1988). Dopamine modifies the balance of rod and cone inputs to horizontal cells of the Xenopus retina. Brain Research 449, 332–336.Google Scholar
Zhang, M., Budak, M.T., Lu, W., Khurana, T.S., Zhang, X., Laties, A.M. & Mitchell, C.H. (2006). Identification of the A3 adenosine receptor in rat retinal ganglion cells. Molecular Vision 12, 937–948.Google Scholar