QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (48) Citing Articles via Google Scholar Google Scholar Articles by Peterson, W. M. Articles by Miller, S. S. Search for Related Content PubMed PubMed Citation Articles by Peterson, W. M. Articles by Miller, S. S.

 Previous Article  |  Next Article 

Volume 17, Number 7, Issue of April 1, 1997 pp. 2324-2337
Copyright ©1997 Society for Neuroscience

Extracellular ATP Activates Calcium Signaling, Ion, and Fluid Transport in Retinal Pigment Epithelium

Received Oct. 10, 1996; revised Jan. 16, 1997; accepted Jan. 21, 1997.

Ward M. Peterson, Chris Meggyesy, Kefu Yu, and Sheldon S. Miller

School of Optometry and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720

The presence of receptors for ATP has not been established in any native preparation of retinal neurons or glia. In the present study, we used conventional electrophysiological and [Ca²⁺]_in fluorescence imaging techniques to investigate the effects of ATP added to Ringer's solution perfusing the retinal-facing (apical) membrane of freshly isolated monolayers of bovine retinal pigment epithelium (RPE). ATP (or UTP) produced large, biphasic voltage and resistance changes with a K_d of ~5 µM for ATP and ~1 µM for UTP. Electrical and pharmacological evidence indicates that the first and second phases of the response are attributable to an increase in basolateral membrane Cl conductance and a decrease in apical membrane K conductance, respectively. The ATP-induced responses were not affected by adenosine, but were reduced by the P₂-purinoceptor blocker suramin. ATP also produced a large, transient increase in [Ca²⁺]_in that was blocked by cyclopiazonic acid, an inhibitor of endoplasmic reticulum Ca²⁺-ATPases. The calcium buffer BAPTA attenuated the voltage effects of ATP. We also found that apical DIDS significantly inhibited the ATP-evoked [Ca²⁺]_in and electrical responses, suggesting that DIDS blocked the purinoceptor. Measurements of fluid movement across the RPE using the capacitance probe technique demonstrated a significant increase in fluid absorption by apical UTP. These data indicate the presence of metabotropic P_2Y/P_2U-purinoceptors at the RPE apical membrane and implicate extracellular ATP in vivo as a retinal signaling molecule that could help regulate the hydration and chemical composition of the subretinal space.

Key words: P_2U-purinoceptor; P_2Y-purinoceptor; electrophysiology; paracrine; K conductance; Cl conductance

This article has been cited by other articles:

				H. C. Hartzell, Z. Qu, K. Yu, Q. Xiao, and L.-T. Chien Molecular Physiology of Bestrophins: Multifunctional Membrane Proteins Linked to Best Disease and Other Retinopathies Physiol Rev, April 1, 2008; 88(2): 639 - 672. [Abstract] [Full Text] [PDF]

				V. E. Tovell and J. Sanderson Distinct P2Y Receptor Subtypes Regulate Calcium Signaling in Human Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 350 - 357. [Abstract] [Full Text] [PDF]

				K. Yu, Z. Qu, Y. Cui, and H. C. Hartzell Chloride Channel Activity of Bestrophin Mutants Associated with Mild or Late-Onset Macular Degeneration Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4694 - 4705. [Abstract] [Full Text] [PDF]

				W. Lu, D. Reigada, J. Sevigny, and C. H. Mitchell Stimulation of the P2Y1 Receptor Up-Regulates Nucleoside-Triphosphate Diphosphohydrolase-1 in Human Retinal Pigment Epithelial Cells J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 157 - 164. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				A. Wurm, T. Pannicke, I. Iandiev, E. Buhner, U.-C. Pietsch, A. Reichenbach, P. Wiedemann, S. Uhlmann, and A. Bringmann Changes in Membrane Conductance Play a Pathogenic Role in Osmotic Glial Cell Swelling in Detached Retinas Am. J. Pathol., December 1, 2006; 169(6): 1990 - 1998. [Abstract] [Full Text] [PDF]

				D. Reigada, W. Lu, and C. H. Mitchell Glutamate acts at NMDA receptors on fresh bovine and on cultured human retinal pigment epithelial cells to trigger release of ATP J. Physiol., September 15, 2006; 575(3): 707 - 720. [Abstract] [Full Text] [PDF]

				A. Maminishkis, S. Chen, S. Jalickee, T. Banzon, G. Shi, F. E. Wang, T. Ehalt, J. A. Hammer, and S. S. Miller Confluent monolayers of cultured human fetal retinal pigment epithelium exhibit morphology and physiology of native tissue. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3612 - 3624. [Abstract] [Full Text] [PDF]

				L. Y. Marmorstein, J. Wu, P. McLaughlin, J. Yocom, M. O. Karl, R. Neussert, S. Wimmers, J. B. Stanton, R. G. Gregg, O. Strauss, et al. The Light Peak of the Electroretinogram Is Dependent on Voltage-gated Calcium Channels and Antagonized by Bestrophin (Best-1) J. Gen. Physiol., April 24, 2006; 127(5): 577 - 589. [Abstract] [Full Text] [PDF]

				D. Reigada, W. Lu, X. Zhang, C. Friedman, K. Pendrak, A. McGlinn, R. A. Stone, A. M. Laties, and C. H. Mitchell Degradation of extracellular ATP by the retinal pigment epithelium Am J Physiol Cell Physiol, September 1, 2005; 289(3): C617 - C624. [Abstract] [Full Text] [PDF]

				D. Reigada and C. H. Mitchell Release of ATP from retinal pigment epithelial cells involves both CFTR and vesicular transport Am J Physiol Cell Physiol, January 1, 2005; 288(1): C132 - C140. [Abstract] [Full Text] [PDF]

				F. Boudreault and R. Grygorczyk Cell swelling-induced ATP release is tightly dependent on intracellular calcium elevations J. Physiol., December 1, 2004; 561(2): 499 - 513. [Abstract] [Full Text] [PDF]

				A. D. Marmorstein, J. B. Stanton, J. Yocom, B. Bakall, M. T. Schiavone, C. Wadelius, L. Y. Marmorstein, and N. S. Peachey A Model of Best Vitelliform Macular Dystrophy in Rats Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3733 - 3739. [Abstract] [Full Text] [PDF]

				T. Irokawa, M. E. Krouse, N. S. Joo, J. V. Wu, and J. J. Wine A "virtual gland" method for quantifying epithelial fluid secretion Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L784 - L793. [Abstract] [Full Text] [PDF]

				M. Nour, A. B. Quiambao, W. M. Peterson, M. R. Al-Ubaidi, and M. I. Naash P2Y2 Receptor Agonist INS37217 Enhances Functional Recovery after Detachment Caused by Subretinal Injection in Normal and rds Mice Invest. Ophthalmol. Vis. Sci., October 1, 2003; 44(10): 4505 - 4514. [Abstract] [Full Text] [PDF]

				S. Blaug, J. Rymer, S. Jalickee, and S. S. Miller P2 purinoceptors regulate calcium-activated chloride and fluid transport in 31EG4 mammary epithelia Am J Physiol Cell Physiol, April 1, 2003; 284(4): C897 - C909. [Abstract] [Full Text] [PDF]

				A. Maminishkis, S. Jalickee, S. A. Blaug, J. Rymer, B. R. Yerxa, W. M. Peterson, and S. S. Miller The P2Y2 Receptor Agonist INS37217 Stimulates RPE Fluid Transport In Vitro and Retinal Reattachment in Rat Invest. Ophthalmol. Vis. Sci., November 1, 2002; 43(11): 3555 - 3566. [Abstract] [Full Text] [PDF]

				C. H. Meyer, K. Hotta, W. M. Peterson, C. A. Toth, and G. J. Jaffe Effect of INS37217, a P2Y2 Receptor Agonist, on Experimental Retinal Detachment and Electroretinogram in Adult Rabbits Invest. Ophthalmol. Vis. Sci., November 1, 2002; 43(11): 3567 - 3574. [Abstract] [Full Text] [PDF]

				W. B. Thoreson, J. S. Ryan, C. Shi, M. E. Kelly, E. J. Bryson, M. L. Toews, T. L. Ediger, and D. M. Chacko Lysophosphatidic Acid Receptor Signaling in Mammalian Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2450 - 2461. [Abstract] [Full Text] [PDF]

				S. Blaug, K. Hybiske, J. Cohn, G. L. Firestone, T. E. Machen, and S. S. Miller ENaC- and CFTR-dependent ion and fluid transport in mammary epithelia Am J Physiol Cell Physiol, August 1, 2001; 281(2): C633 - C648. [Abstract] [Full Text] [PDF]

				J. Rymer, S. S. Miller, and J. L. Edelman Epinephrine-Induced Increases in [Ca2+]in and KCl-Coupled Fluid Absorption in Bovine RPE Invest. Ophthalmol. Vis. Sci., July 1, 2001; 42(8): 1921 - 1929. [Abstract] [Full Text] [PDF]

				R. H. Quinn, J. N. Quong, and S. S. Miller Adrenergic Receptor Activated Ion Transport in Human Fetal Retinal Pigment Epithelium Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 255 - 264. [Abstract] [Full Text]

				N. K. Wills, T. Weng, L. Mo, H. L. Hellmich, A. Yu, T. Wang, S. Buchheit, and B. F. Godley Chloride Channel Expression in Cultured Human Fetal RPE Cells: Response to Oxidative Stress Invest. Ophthalmol. Vis. Sci., December 1, 2000; 41(13): 4247 - 4255. [Abstract] [Full Text]

				H. Sauer, J. Hescheler, and M. Wartenberg Mechanical strain-induced Ca2+ waves are propagated via ATP release and purinergic receptor activation Am J Physiol Cell Physiol, August 1, 2000; 279(2): C295 - C307. [Abstract] [Full Text] [PDF]

				V. Ralevic and G. Burnstock Receptors for Purines and Pyrimidines Pharmacol. Rev., September 1, 1998; 50(3): 413 - 492. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help