Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-23T07:44:15.907Z Has data issue: false hasContentIssue false

Intracellular organelles and calcium homeostasis in rods and cones

Published online by Cambridge University Press:  06 November 2007

TAMAS SZIKRA
Affiliation:
Department of Ophthalmology, UCSF School of Medicine, San Francisco, California Current address: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, WRO-1066-4-46, Basel-4058, Switzerland.
DAVID KRIŽAJ
Affiliation:
Department of Ophthalmology, UCSF School of Medicine, San Francisco, California Department of Ophthalmology, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah

Abstract

The role of intracellular organelles in Ca2+ homeostasis was studied in salamander rod and cone photoreceptors under conditions that simulate photoreceptor activation by darkness and light. Sustained depolarization evoked a Ca2+ gradient between the cell body and ellipsoid regions of the inner segment (IS). The standing pattern of calcium fluxes was created by interactions between the plasma membrane, endoplasmic reticulum (ER), and mitochondria. Pharmacological experiments suggested that mitochondria modulate both baseline [Ca2+]i in hyperpolarized cells as well as kinetics of Ca2+ entry via L type Ca2+ channels in cell bodies and ellipsoids of depolarized rods and cones. Inhibition of mitochondrial Ca2+ sequestration by antimycin/oligomycin caused a three-fold reduction in the amount of Ca2+ accumulated into intracellular organelles in both cell bodies and ellipsoids. A further 50% decrease in intracellular Ca2+ content within cell bodies, but not ellipsoids, was observed after suppression of SERCA-mediated Ca2+ uptake into the ER. Inhibition of Ca2+ sequestration into the endoplasmic reticulum by thapsigargin or cyclopiazonic acid decreased the magnitude and kinetics of depolarization-evoked Ca2+ signals in cell bodies of rods and cones and decreased the amount of Ca2+ accumulated into internal stores. These results suggest that steady-state [Ca2+]i in photoreceptors is regulated in a region-specific manner, with the ER contribution predominant in the cell body and mitochondrial buffering [Ca2+] the ellipsoid. Local [Ca2+]i levels are set by interactions between the plasma membrane Ca2+ channels and transporters, ER and mitochondria. Mitochondria are likely to play an essential role in temporal and spatial buffering of photoreceptor Ca2+.

Type
Research Article
Copyright
© 2007 Cambridge University Press

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

REFERENCES

Almers, W. & Neher, E. (1985). The Ca signal from fura-2 loaded mast cells depends strongly on the method of dye-loading. FEBS Lett. 192, 1318.Google Scholar
Babcock, D.F. & Hille, B. (1998). Mitochondrial oversight of cellular Ca2+ signaling. Current Opinions in Neurobiology 8, 398404.Google Scholar
Bader, C.R., Bertrand, D. & Schwartz, E.A. (1982). Voltage-activated and calcium-activated currents studied in solitary rod inner segments from the salamander retina. Journal of Physiology 331, 25322584.Google Scholar
Berridge, M.J., Bootman, M.D. & Roderick, H.L. (2003). Calcium signalling: Dynamics, homeostasis and remodelling. Nature Reviews Molecular Cell Biology 4, 517529.Google Scholar
Budd, S.L. & Nicholls, D.G. (1996). A reevaluation of the role of mitochondria in neuronal Ca2+ homeostasis. Journal of Neurochemistry 66, 403411.Google Scholar
Cadetti, L., Bryson, E.J., Ciccone, C.A., Rable, K. & Thoreson, W.B. (2006). Calcium-induced calcium release in rod photoreceptor terminal boosts synaptic transmission during maintained depolarization. European Journal of Neuroscience 23, 29832990.Google Scholar
Cao, L. & Eldred, W.D. (2001). Subcellular localization of neuronal nitric oxide synthase in turtle retina: Electron immunocytochemistry. Visual Neuroscience 18, 949960.Google Scholar
Chang, G.Q., Hao, Y. & Wong, F. (1993). Apoptosis: Final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice. Neuron 11, 595605.Google Scholar
Chiarini, L.B., Leal-Ferreira, M.L., de Freitas, F.G. & Linden, R. (2003). Changing sensitivity to cell death during development of retinal photoreceptors. Journal of Neuroscience Research 74, 875883.Google Scholar
Cooper, L.L., Hansen, R.M., Darras, B.T., Korson, M., Dougherty, F.E., Shoffner, J.M. & Fulton, A.B. (2002). Rod photoreceptor function in children with mitochondrial disorders. Archive of Ophthalmology 120, 10551062.Google Scholar
Demaurex, N., Lew, D.P. & Krause, K.H. (1992). Cyclopiazonic acid depletes intracellular Ca2+ stores and activates an influx pathway for divalent cations in HL-60 cells. Journal of Biological Chemistry 267, 23182324.Google Scholar
Donovan, M. & Cotter, T.G. (2002). Caspase-independent photoreceptor apoptosis in vivo and differential expression of apoptotic protease activating factor-1 and caspase-3 during retinal development. Cell Death and Differentiation 9, 12201231.Google Scholar
Doonan, F., Donovan, M. & Cotter, T.G. (2005). Activation of multiple pathways during photoreceptor apoptosis in the rd mouse. Investigative Ophthalmology & Visual Science 46, 35303538.Google Scholar
Duchen, M.R. (1999). Contributions of mitochondria to animal physiology: From homeostatic sensor to calcium signalling and cell death. Journal of Physiology 516, 117.Google Scholar
Fain, G.L., Matthews, H.R., Cornwall, M.C. & Koutalos, Y. (2001). Adaptation in vertebrate photoreceptors. Physiological Reviews 81, 117151.Google Scholar
Fliesler, S.J., Richards, M.J., Miller, C.Y., Mckay, S. & Winkler, B.S. (1997). In vitro metabolic competence of the frog retina: Effects of glucose and oxygen deprivation. Experimental Eye Research 64, 683692.Google Scholar
Hajnoczky, G., Davies, E. & Madesh, M. (2003). Calcium signaling and apoptosis. Biochemical and Biophysical Research Communications 304, 445454.Google Scholar
Haugh-Scheidt, L.M., Linsenmeier, R.A. & Griff, E.R. (1995). Oxygen consumption in the isolated toad retina. Experimental Eye Research 61, 6372.Google Scholar
He, L., Poblenz, A.T., Medrano, C.J. & Fox, D.A. (2000). Lead and calcium produce rod photoreceptor cell apoptosis by opening the mitochondrial permeability transition pore. Journal of Biological Chemistry 275, 1217512184.Google Scholar
Heidelberger, R., Thoreson, W.B. & Witkovsky, P. (2005). Synaptic transmission at retinal ribbon synapses. Progress in Retinal Eye Research 24, 682720.Google Scholar
Hernandez-Guijo, J.M., Maneu-Flores, V.E., Ruiz-Nuno, A., Villarroya, M., Garcia, A.G. & Gandia, L. (2001). Calcium-dependent inhibition of L, N, and P/Q Ca2+ channels in chromaffin cells: Role of mitochondria. Journal of Neuroscience 21, 255325560.Google Scholar
Hoang, Q.V., Linsenmeier, R.A., Chung, C.K. & Curcio, C.A. (2002). Photoreceptor inner segments in monkey and human retina: Mitochondrial density, optics, and regional variation. Visual Neuroscience 19, 395407Google Scholar
Hoth, M., Button, D.C. & Lewis, R.S. (2000). Mitochondrial control of calcium-channels gating: A mechanism for sustained signaling and transcriptional activation in T lymphocytes. Proceedings of the National Academy of Sciences United States of America 97, 1060710612.Google Scholar
Inesi, G. & Sagara, Y. (1994). Specific inhibitors of intracellular Ca2+ transport ATPases. Journal of Membrane Biology 141, 16.Google Scholar
Jouaville, L.S., Pinton, P., Bastianutto, C., ogyutter, G.A. & Rizzuto, R. (1999). Regulation of mitochondrial ATP synthesis by calcium: Evidence for a long-term metabolic priming. Proceedings of the National Academy of Sciences United States of America 96, 1380713812.Google Scholar
Kimble, E.A., Svoboda, R.A. & Ostroy, S.E. (1980). Oxygen consumption and ATP changes of the vertebrate photoreceptor. Experimental Eye Research 31, 271288.Google Scholar
Križaj, D., Bao, J.X., Schmitz, Y., Witkovsky, P. & Copenhagen, D.R. (1999). Caffeine-sensitive calcium stores regulate synaptic transmission from retinal rod photoreceptors. Journal of Neuroscience 19, 72497261.Google Scholar
Križaj, D. & Copenhagen, D.R. (1998). Compartmentalization of calcium extrusion mechanisms in the outer and inner segments of photoreceptors. Neuron 21, 249256.Google Scholar
Križaj, D. & Copenhagen, D.R. (2002). Calcium regulation in photoreceptors. Front Bioscience 7, d2023d2044.Google Scholar
Križaj, D., Lai, F.A. & Copenhagen, D.R. (2003). Ryanodine stores and calcium regulation in the inner segments of salamander rods and cones. Journal of Physiology 547, 761774.Google Scholar
Križaj, D., Liu, X.L. & Copenhagen, D.R. (2004). Expression of calcium transporters in the retina of the tiger salamander (Ambystoma tigrinum). Journal of Comparative Neurology 475, 463480.Google Scholar
Landolfi, B., Curci, S., Debellis, L., Pozzan, T. & Hofer, A.M. (1998). Ca2+ homeostasis in the agonist-sensitive internal store: Functional interactions between mitochondria and the ER measured In situ in intact cells. Journal of Cell Biology 142, 12351243.Google Scholar
Mariani, A.P. (1986). Photoreceptors of the salamander retina. Journal of Comparative Neurology 247, 497504.Google Scholar
Martin, V., Bredoux, R., Corvazier, E., Van Gorp, R., Kovàcs, T., Gélébart, P. & Enouf, J. (2002). Three novel sarco/endoplasmic reticulum Ca2+ATPase (SERCA) 3 isoforms. Expression, regulation and function of the members of the SERCA3 family. Journal of Biological Chemistry 277, 2444224452.Google Scholar
Mattson, M.P. & Chan, S.L. (2003). Calcium orchestrates apoptosis. Natural Cell Biology 5, 10411043.Google Scholar
Medler, K. & Gleason, E.L. (2002). Mitochondrial Ca(2+) buffering regulates synaptic transmission between retinal amacrine cells. Journal of Neurophysiology 87, 14261439.Google Scholar
Mercurio, A.M. & Holtzman, E. (1982). Smooth endoplasmic reticulum and other agranular reticulum in frog retinal photoreceptors. Journal of Neurocytology 11, 263293.Google Scholar
Montero, M., Alonso, M.T., Carnicero, E., Cuchillo-Ibanez, I., Albillos, A., Garcia, A.G., Garcia-Sancho, J. & Alvarez, J. (2000). Chromaffin-cell stimulation triggers fast milimolar mitochondrial Ca2+ transients that modulate secretion. Nature Cell Biology 2, 5761.Google Scholar
Nachman-Clewner, M., St. Jules, R. & Townes-Anderson, E. (1999). L-type calcium channels in the photoreceptor ribbon synapse: Localization and role in plasticity. Journal of Comparative Neurology 415, 116.Google Scholar
Neher, E. (1995). The use of fura-2 for estimating Ca buffers and Ca fluxes. Neuropharmacology 34, 14231442.Google Scholar
Nilsson, S.E. (1985). The retinal photoreceptors and the pigment epithelium. Structure and function. Transduction. Acta Ophthalmology Supplemental 173, 48.Google Scholar
Pendergrass, W., Wolf, N. & Poot, M. (2004). Efficacy of mitotracker green and CMX rosamine to measure changes in mitochondrial membrane potentials in living cells and tissues. Cytometry 61, 162169.Google Scholar
Rieke, F. & Schwartz, E.A. (1994). A cGMP-gated current can control exocytosis at cone synapses. Neuron 13, 863873.Google Scholar
Rieke, F. & Schwartz, E.A. (1996). Asynchronous transmitter release: Control of exocytosis and endocytosis at the salamander rod synapse. Journal of Physiology 493, 18.Google Scholar
Rizzuto, R., Duchen, M.R. & Pozzan, T. (2004). Flirting in little space: The ER/mitochondria Ca2+ liaison. Signal Transduction Knowledge Environment 215, re1.Google Scholar
Scaduto, R.C. & Grotyohann, L.W. (1999). Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophysics Journal 76, 469477.Google Scholar
Scotti, A.L., Chatton, J.Y. & Reuter, H. (1999). Roles of Na(+)-Ca2+ exchange and of mitochondria in the regulation of presynaptic Ca2+ and spontaneous glutamate release. Philosophical Transactions of the Royal Society of London 354, 357364.Google Scholar
Somlyo, A.P. & Walz, B. (1985). Elemental distribution in Rana pipiens retinal rods: Quantitative electron probe study. Journal of Physiology 358, 183195.Google Scholar
Steele, E.C., Chen, X., Iuvone, P.M. & MacLeish, P.R. (2005). Imaging of Ca2+ dynamics within the presynaptic terminals of salamander rod photoreceptors. Journal of Neurophysiology 94, 45444553.Google Scholar
Suryanarayanan, A. & Slaughter, M.M. (2006). Synaptic transmission mediated by internal calcium stores in rod photoreceptors. Journal of Neuroscience 26, 17591766.Google Scholar
Szikra, T., Cusato, K. & Križaj, D. (2006). Store-operated channels regulate baseline Ca in light-adapted photoreceptors. Investigative Ophthalmology & Visual Science 47, 3715a.Google Scholar
Szikra, T. & Križaj, D. (2006). The dynamic range and domain-specific signals of intracellular calcium in photoreceptors. Neuroscience 141, 143155Google Scholar
Tinel, H., Cancela, J.M., Mogami, H., Gerasimenko, J.V., Gerasimenko, O.V., Tepikin, A.V. & Petersen, O.H. (1999). Active mitochondria surronding the pancreatic acinar granule region prevent spreading of inositol triphosphate-evoked local cytosolic Ca(2+) signals. The European Molecular Biology Organization Journal 18, 49995008.Google Scholar
Townes-Anderson, E., MacLeish, P.R. & Raviola, E. (1985). Rod cells dissociated from mature salamander retina: Ultrastructure and uptake of horseradish peroxidase. Journal of Cell Biology 100, 175188.Google Scholar
Treiman, M., Caspersen, C. & Christensen, S.B. (1998). A tool coming of age: Thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPases. Trends in Pharmacological Sciences 19, 131135.Google Scholar
Ungar, F., Piscopo, I. & Holtzman, E. (1981). Calcium accumulation in intracellular compartments of from retinal rod photoreceptors. Brain Research 205, 200206.Google Scholar
Ungar, F., Piscopo, I., Letizia, J. & Holtzman, E. (1984). Uptake of calcium by the endoplasmic reticulum of frog the frog photoreceptor. Journal of Cell Biology 98, 16451655.Google Scholar
Uyama, Y., Imaizumi, Y. & Watanabe, M. (1992). Effects of cyclopiazonic acid, a novel Ca(2+) ATPase inhibitor, on contractile responses in skinned ileal smooth muscle. British Journal of Pharmacology 106, 208214.Google Scholar
Verkhratsky, A. (2005). Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiological Reviews 85, 201279.Google Scholar
Walz, B. & Baumann, O. (1995). Structure and cellular physiology of Ca2+ stores in invertebrate photoreceptors. Cell Calcium 18, 342351.Google Scholar
White, R.J. & Reynolds, I.J. (1996). Mitochondrial depolarization in glutamate-stimulated neurons: An early signal specific to excitotoxin exposure. Journal of Neuroscience 16, 56885697.Google Scholar
Winkler, B.S. (1975). Dependence of rat and rabbit photoreceptor potentials upon anaerobic and aerobic metabolism in vitro. Experimental Eye Research 21, 545548Google Scholar
Winkler, B.S. (1983). Relative inhibitory effects of ATP depletion, ouabain and calcium on retinal photoreceptors. Experimental Eye Research 36, 581594.Google Scholar
Winkler, B.S., Sauer, M.W. & Starnes, C.A. (2003). Modulation of the Pasteur effect in retinal cells: Implications for understanding compensatory metabolic mechanisms. Experimental Eye Research 76, 715723.Google Scholar
Zhang, N. & Townes-Anderson, E. (2002). Regulation of structural plasticity by different channel types in rod and cone photoreceptors. Journal of Neuroscience 22, 70657079.Google Scholar