Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-10T16:47:41.277Z Has data issue: false hasContentIssue false
  • English
  • Français

Purinergic modulation of frog electroretinographic responses: The role of the ionotropic receptor P2X7

Published online by Cambridge University Press:  31 July 2017

PETIA KUPENOVA ,
ELKA POPOVA  and
LILIYA VITANOVA
PETIA KUPENOVA*
Affiliation:
Department of Physiology, Medical University of Sofia, Sofia, Bulgaria
ELKA POPOVA
Affiliation:
Department of Physiology, Medical University of Sofia, Sofia, Bulgaria
LILIYA VITANOVA
Affiliation:
Department of Physiology, Medical University of Sofia, Sofia, Bulgaria
*
*Address correspondence to: Petia Kupenova, Department Physiology, Medical University of Sofia, 1 G. Sofiiski St., Sofia 1431, Bulgaria. E-mail: pkupenova@abv.bg
Get access Rights & Permissions [Opens in a new window]

Abstract

The contribution of the purinergic receptors P2X7 (P2X7Rs) to the electroretinographic (ERG) responses was studied by testing the effects of the selective P2X7R antagonist A438079 and the selective P2X7R agonist Bz-ATP on the electroretinograms obtained in perfused frog (Rana ridibunda) eyecup preparations under a variety of stimulation conditions. The P2X7R blockade by 200 µM A438079 diminished the amplitude of the photoreceptor components: the a-wave and the pharmacologically isolated mass receptor potential. In the pure rod-driven and pure cone-driven responses, the amplitude of the postreceptoral ON (b-wave) and OFF (d-wave) components was also diminished. The OFF responses were affected to a greater extent compared to the ON responses. In the mixed rod- and cone-driven responses, obtained in the mesopic intensity range, the b-wave amplitude was increased, while the d-wave amplitude was decreased. The amplitude of the oscillatory potentials was diminished. The relative amplitude changes produced by the P2X7R blockade were greater in the dark-adapted compared to the light-adapted eyes. The application of 100 µM Bz-ATP produced small effects opposite to those of the antagonist, while a prolonged (>20 min) treatment with 1 mM Bz-ATP resulted in a significant amplitude reduction or even abolishment of b- and d-waves. Our results show that endogenous ATP through its P2X7Rs exerts significant, mostly potentiating effects on the ERG photoreceptor and postreceptoral responses. There is a clear ON/OFF asymmetry of the effects on the ERG postreceptoral responses favoring OFF responses: they are always strongly potentiated, while the ON responses are either less potentiated (in the rod-driven and most of the cone-driven responses) or even inhibited (in the mixed rod- and cone-driven responses). The overstimulation of P2X7Rs can produce acute pathological changes, that is, a decrease or abolishment of the ERG responses.

Keywords

P2X7PurinergicERGA438079Bz-ATP
Type
Research Article
Information
Visual Neuroscience , Volume 34 , 2017 , E015
Copyright
Copyright © Cambridge University Press 2017 

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.)

References

Abbracchio, M.P., Burnstock, G., Verkhratsky, A. & Zimmermann, H. (2009). Purinergic signalling in the nervous system: An overview. Trends in Neurosciences 32(1), 19–29.Google Scholar
Aplin, F.P., Luu, C.D., Vessey, K.A., Guymer, R.H., Shepherd, R.K. & Fletcher, E.L. (2014). ATP-induced photoreceptor death in a feline model of retinal degeneration. Investigative Ophthalmology & Visual Science 55, 8319–8329.Google Scholar
Alves, L.A., De Melo Reis, R.A., De Souza, C.A.M., De Freitas, M.S., Teixeira, P.C., Neto Moreira Ferreira, D. & Xavier, R.F. (2014). The P2X7 receptor: Shifting from a low- to a high-conductance channel—An enigmatic phenomenon? Biochimica et Biophysica Acta 1838(10), 2578–2587.Google Scholar
Attwell, D., Werblin, F.S., Wilson, M. & Wu, S.M. (1983). A sign-reversing pathway from rods to double and single cones in the retina of the tiger salamander. The Journal of Physiology 336, 313–333.Google Scholar
Awatramani, G., Wang, J. & Slaughter, M.M. (2001). Amacrine and ganglion cell contributions to the electroretinogram in amphibian retina. Visual Neuroscience 18, 147–156.Google Scholar
Bartlett, R., Stokes, L. & Sluyter, R. (2014). The P2X7 receptor channel: Recent developments and the use of P2X7 antagonists in models of disease. Pharmacological Reviews 66, 638–675.CrossRefGoogle ScholarPubMed
Bianchi, B.R., Lynch, K.J., Touma, E., Niforatos, W., Burgard, E.C., Alexander, K.M., Park, H.S., Yu, H., Metzger, R., Kowaluk, E., Jarvis, M.F. & Van Biesen, T. (1999). Pharmacological characterization of recombinant human and rat P2X receptor subtypes. European Journal of Pharmacology 376(1–2), 127–138.Google Scholar
Brändle, U., Kohler, K. & Wheeler-Schilling, T.H. (1998). Expression of the P2X7-receptor subunit in neurons of the rat retina. Molecular Brain Research 62(1), 106–109.Google Scholar
Bringmann, A., Pannicke, T., Moll, V., Milenkovic, I., Faude, F., Enzmann, V., Wolf, S. & Reichenbach, A. (2001). Upregulation of P2X7 receptor currents in Müller glial cells during proliferative vitreoretinopathy. Investigative Ophthalmology & Visual Science 42(3), 860–867.Google Scholar
Bui, B. & Fortune, B. (2004). Ganglion cell contributions to the rat full-field electroretinogram. The Journal of Physiology 555(1), 153–173.CrossRefGoogle Scholar
Chavda, S., Luthert, P.J. & Salt, T.E. (2016). P2X7R modulation of visually evoked synaptic responses in the retina. Purinergic Signalling 12, 611.Google Scholar
Coddou, C., Yan, Z., Obsil, T., Pablo Huidobro-Toro, J. & Stojilkovic, S.S. (2001). Activation and regulation of purinergic P2X receptor channels. Pharmacological Reviews 63(3), 641–683.Google Scholar
Dong, C-J. & Hare, W.A. (2000). Contribution to the kinetics and amplitude of the electroretinogram b-wave by third order retinal neurons in the rabbit retina. Vision Research 40, 579–589.Google Scholar
Dong, C-J. & Hare, W.A. (2002). GABAc feedback pathway modulates the amplitude and kinetics of ERG b-wave in a mammalian retina in vivo . Vision Research 42, 1081–1087.Google Scholar
Dong, C.J., Qian, H.H., McReynolds, J.S., Yang, X.L. & Liu, Y.M. (1988). Suppression of cone-driven responses by rods in the isolated frog retina. Visual Neuroscience 1(4), 331–338.CrossRefGoogle ScholarPubMed
Donnelly-Roberts, D.L., Namovic, M.T., Han, P. & Jarvis, M.F. (2009). Mammalian P2X7 receptor pharmacology: Comparison of recombinant mouse, rat and human P2X7 receptors. British Journal of pharmacology 157(7), 1203–1214.Google Scholar
Donner, K.O. & Reuter, T. (1976). Visual pigments and photoreceptor function. In Frog Neurobiology. A Handbook, ed. Llinas, R. & Precht, W., pp. 251–258. Berlin, Heidelberg: Springer-Verlag.Google Scholar
Dowling, J.E. & Werblin, F.S. (1969). Organization of retina of the mudpuppy, necturus maculosus. I. Synaptic structure. Journal of Neurophysiology XXXII(3), 315–338.Google Scholar
Fain, G.L. (1975). Interactions of rod and cone signals in the mudpuppy retina. The Journal of Physiology 252, 735–769.Google Scholar
Fain, G.L. (1976). Sensitivity of toad rods: Dependence on wave-length and background illumination. The Journal of Physiology 261, 71–101.Google Scholar
Falk, G. (1988). Signal transmission from rods to bipolar and horizontal cells: A synthesis. Progress in Retinal Research 8, 255–279.Google Scholar
Govardovskii, V.I., Fyhrquist, N., Reuter, T., Kuzmin, D.G. & Donner, K. (2000). In search of the visual pigment template. Visual Neuroscience 17(4), 509–528.CrossRefGoogle ScholarPubMed
Gurevich, L. & Slaughter, M.M. (1993). Comparison of the waveforms of the on bipolar neuron and the b-wave of the electroretinogram. Vision Research 33(17), 2431–2435.Google Scholar
Hanitzsch, R. (1981). Dependence of the b-wave on the potassium concentration in the isolated superfused rabbit retina. Documenta Ophthalmologica 51(3), 235–240.CrossRefGoogle ScholarPubMed
Hanitzsch, R., Küppers, L. & Flade, A. (2004). The effect of GABA and the GABA-uptake-blocker NO-711 on the b-wave of the ERG and the responses of horizontal cells to light. Graefe’s Archive of Clinical and Experimental Ophthalmology 242, 784–791.Google Scholar
Ishii, K., Kaneda, M., Li, H., Rockland, K.S. & Hashikawa, T. (2003). Neuron-specific distribution of P2X7 purinergic receptors in the monkey retina. The Journal of Comparative Neurology 459, 267–277.Google Scholar
Kaneda, M., Ishii, K., Morishima, Y., Akagi, T., Yamazaki, Y., Nakanishi, S. & Hashikawa, T. (2004). Off-cholinergic-pathway-selective localization of P2X2 purinoceptors in the mouse retina. Journal of Comparative Neurology 476(1), 103–111.Google Scholar
Karwoski, C.J., Xu, X. & Yu, H. (1996). Current-source density analysis of the electroretinogram of the frog: Methodological issues and origin of components. Journal of Optical Society of America A 13(3), 549–556.CrossRefGoogle ScholarPubMed
Khadra, A., Tomić, M., Yan, Z., Zemkova, H., Sherman, A. & Stojilkovic, S.S. (2013). Dual gating mechanism and function of P2X7 receptor channels. Biophysical Journal 104(12), 2612–2621.Google Scholar
Kupenova, T. (2011). An inductive algorithm for smooth approximation of functions. Communication of the Joint Institute for Nuclear Research, Dubna E11-2011-97.Google Scholar
Lasansky, A. (1973). Organization of the outer synaptic layer in the retina of the larval tiger salamander. Philosophical Transactions of the Royal Society B: Biological Sciences 265, 471–489.Google ScholarPubMed
Li, Y., Holtzclaw, L.A. & Russell, J.T. (2001). Müller cell Ca2+ waves evoked by purinergic receptor agonists in slices of rat retina. Journal of Neurophysiology 85, 986–994.Google Scholar
Mitchell, C.H. (2001). Release of ATP by a human retinal pigment epithelial cell line: Potential for autocrine stimulation through subretinal space. Journal of Physiology 534(1), 193–202.Google Scholar
Mitchell, C.H. & Reigada, D. (2008). Purinergic signalling in the subretinal space: A role in the communication between the retina and the RPE. Purinergic Signalling 4(2), 101–107.Google Scholar
Murakami, M., Ohtsu, K. & Ohtsuka, T. (1972). Effects of chemicals on receptors and horizontal cells in the retina. Journal of Physiology 227(3), 899–913.Google Scholar
Neal, M. & Cunningham, J. (1994). Modulation by endogenous ATP of the light-evoked release of ACh from retinal cholinergic neurons. British Journal of Pharnacology 113, 1085–1087.Google Scholar
Newman, E.A. (2004a). Glial modulation of synaptic transmission in the retina. GLIA 47(3), 268–274.Google Scholar
Newman, E.A. (2004b). A dialogue between glia and neurons in the retina: Modulation of neuronal excitability. Neuron Glia Biology 1(3), 245–252.Google Scholar
Normann, R.A. & Werblin, F.S. (1974). Control of retinal sensitivity. I. Light and dark adaptation of vertebrate rods and cones. The Journal of General Physiology 63, 37–61.Google Scholar
Pannicke, T., Fischer, W., Biedermann, B., Schädlich, H., Grosche, J., Faude, F., Wiedemann, P., Allgaier, C., Illes, P., Burnstock, G. & Reichenbach, A. (2000). P2X7 receptors in Müller glial cells from the human retina. Journal of Neuroscience 20(16), 5965–5972.Google Scholar
Popova, E. & Kupenova, P. (2009). Contribution of proximal retinal neurons to b- and d-waves of frog electroretinogram under different conditions of light adaptation. Vision Research 49, 2001–2010.Google Scholar
Popova, E. & Kupenova, P. (2011). Effects of dopamine D1 receptor blockade on the intensity–response function of ERG b- and d-waves under different conditions of light adaptation. Vision Research 51, 1627–1636.Google Scholar
Puthussery, T. & Fletcher, E.L. (2004). Synaptic localization of P2X7 receptors in the rat retina. Journal of Comparative Neurology 472(1), 13–23.CrossRefGoogle ScholarPubMed
Puthussery, T. & Fletcher, E. (2009). Extracellular ATP induces retinal photoreceptor apoptosis through activation of purinoceptors in rodents. Journal of Comparative Neurology 513(4), 430–440.Google Scholar
Puthussery, T., Yee, P., Vingrys, A.J. & Fletcher, E.L. (2006). Evidence for the involvement of purinergic P2X7 receptors in outer retinal processing. European Journal of Neuroscience 24, 7–19.Google Scholar
Reichenbach, A. & Bringmann, A. (2016). Purinergic signaling in retinal degeneration and regeneration. Neuropharmacology 104, 194–211.Google Scholar
Santos, P.F., Caramelo, O.L., Carvalho, A.P. & Duarte, C.B. (1999). Characterization of ATP release from cultures enriched in cholinergic amacrine-like neurons. Journal of neurobiology 41(3), 340–348.Google Scholar
Sillman, A.J., Ito, H. & Tomita, T. (1969a). Studies on the mass receptor potential of the isolated frog retina I. General properties of the response. Vision Research 9, 1435–1442.Google Scholar
Sillman, A.J., Ito, H. & Tomita, T. (1969b). Studies on the mass receptor potential of the isolated frog retina II. On the basis of the ionic mechanism. Vision Research 9, 1443–1451.Google Scholar
Skaper, S.D., Debetto, P. & Giusti, P. (2010). The P2X7 purinergic receptor: From physiology to neurological disorders. FASEB Journal 24(2), 337–345.CrossRefGoogle ScholarPubMed
Sperlágh, B. & Illes, P. (2014). P2X7 receptor: An emerging target in central nervous system diseases. Trends in Pharmacological Sciences 35(10), 537–5 54.Google Scholar
Sperlágh, B., Vizi, E.S., Wirkner, K. & Illes, P. (2006). P2X7 receptors in the nervous system. Progress in Neurobiology 78(6), 327–346.Google Scholar
Stockton, R.A. & Slaughter, M.M. (1989). B-wave of the electroretinogram. A reflection of on-bipolar cell activity. The Journal of General Physiology 93, 101–122.Google Scholar
Sugiyama, T. (2014). Role of P2X7 receptors in the development of diabetic retinopathy. World Journal of Diabetes 5(2), 141–145.CrossRefGoogle ScholarPubMed
Surprenant, A., Rassendren, F., Kawashima, E., North, R.A. & Buell, G. (1996). The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272(5262), 735–738.Google Scholar
Talmi, A. & Gilat, G. (1977). Method for smooth approximation of data. Journal of Computational Physics 23(2), 93–123.Google Scholar
Ueno, S., Kondo, M., Ueno, M., Miyata, K., Terasaki, H. & Miyake, Y. (2006). Contribution of retinal neurons to d-wave of primate photopic electroretinograms. Vision Research 46, 658–664.Google Scholar
Vessey, K.A. & Fletcher, E.L. (2012). Rod and cone pathway signalling is altered in the P2X7 receptor knock out mouse. PLoS ONE 7(1), e29990.Google Scholar
Vessey, K.A., Greferath, U., Aplin, F.P., Jobling, A.I., Phipps, J.A., Ho, T., De Iongh, R.U. & Fletcher, E.L. (2014). Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats. The Journal of Comparative Neurology 522(13), 2928–2950.Google Scholar
Vitanova, L. & Kupenova, P. (2014). Ionotropic purinergic receptors P2X in frog and turtle retina: Glial and neuronal localization. Acta Histochemica 116(5), 694–701.Google Scholar
Volonté, C., Apolloni, S., Skaper, S.D. & Burnstock, G. (2012). P2X7 receptors: Channels, pores and more. CNS and Neurological Disorders - Drug Targets 11(6), 705–721.Google Scholar
Wachtmeister, L. (2001). Some aspects of the oscillatory response of the retina. In Progress in Brain Research, Vol. 131, ed. Kolb, H. & Wu, S., pp. 465–474. Amsterdam, Netherlands: Elsevier Science B.V.Google Scholar
Wakx, A., Dutot, M., Massicot, F., Mascarelli, F., Limb, G.A. & Rat, P. (2016). Amyloid β peptide induces apoptosis through P2X7 cell death receptor in retinal cells: Modulation by marine omega-3 fatty acid DHA and EPA. Applied Biochemistry and Biotechnology 178, 368–381.Google Scholar
Wheeler-Schilling, T.H., Marquordt, K., Kohler, K., Jabs, R. & Guenther, E. (2000). Expression of purinergic receptors in bipolar cells of the rat retina. Molecular Brain Research 76(2), 415–418.Google Scholar
Wheeler-Schilling, T.H., Marquordt, K., Kohler, K., Guenther, E. & Jabs, R. (2001). Identification of purinergic receptors in retinal ganglion cells. Molecular Brain Research 92(1–2), 177–180.Google Scholar
Wurm, A., Pannicke, T., Iandiev, I., Francke, M., Hollborn, M., Wiedemann, P., Reichenbach, A., Osborne, N.N. & Bringmann, A. (2011). Purinergic signaling involved in Müller cell function in the mammalian retina. Progress in Retinal and Eye Research 30(5), 324–342.Google Scholar
Xu, X. & Karwoski, C.J. (1994). Current source density analysis of retinal field potentials. II. Pharmacological analysis of the b-wave and M-wave. Journal of Neurophysiology 72, 96–105.Google Scholar
Xu, X. & Karwoski, C.J. (1995). Current source density analysis of the electroretinographic d-wave of frog retina. Journal of Neurophysiology 73, 2459–2469.Google Scholar
Yan, Z., Khadra, A., Li, S., Tomić, M., Sherman, A. & Stojilkovic, S.S. (2010). Experimental characterization and mathematical modeling of P2X7 receptor channel gating. Journal of Neuroscience 30(42), 14213–14224.Google Scholar
Yanagida, T., Koshimizu, M., Kawasaki, K. & Yonemura, D. (1986). Microelectrode depth study of electroretinographic b- and d-waves in frog retina. Japanese Journal of Ophthalmology 30, 298–305.Google Scholar
Yang, D. & Chen, J. (2014). The P2X7 receptor in AMD. Austin Journal of Clinical Ophthalmology 1(3), 1012.Google Scholar
Yang, D., Elner, S.G., Clark, A.J., Hugbes, B.A., Petty, H.R. & Elner, V.M. (2011). Activation of P2X receptors induces apoptosis in human retinal pigment epithelium. Investigative Ophthalmology & Visual Science 52(3), 1522–1530.Google Scholar