July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
ATP-induced alterations in extracellular H+: a potent potential mechanism for modulation of neuronal signals by Müller (glial) cells in the vertebrate retina.
Author Affiliations & Notes
  • Robert Paul Malchow
    Biological Sciences & Ophthalmology, University of Illinois at Chicago, Chicago, Illinois, United States
  • Boriana K Tchernookova
    Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Lars Holzhausen
    Molecular and Cell Biology, University of California at Berkeley, Berkeley, California, United States
  • Richard H Kramer
    Molecular and Cell Biology, University of California at Berkeley, Berkeley, California, United States
  • Matthew A Kreitzer
    Biology, Indiana Wesleyan University, Marion, Indiana, United States
  • Footnotes
    Commercial Relationships   Robert Malchow, None; Boriana Tchernookova, None; Lars Holzhausen, None; Richard Kramer, None; Matthew Kreitzer, None
  • Footnotes
    Support  NSF grants 1557820 & 1557725
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1863. doi:
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      Robert Paul Malchow, Boriana K Tchernookova, Lars Holzhausen, Richard H Kramer, Matthew A Kreitzer; ATP-induced alterations in extracellular H+: a potent potential mechanism for modulation of neuronal signals by Müller (glial) cells in the vertebrate retina.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1863.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Small alterations in extracellular acidity are potent modulators of neuronal signaling within the vertebrate retina. We have examined the effects of extracellular ATP on extracellular H+ fluxes of isolated Müller cells and changes in H+ levels in retinal slices and intact retinae

Methods : Self-referencing H+-selective microelectrodes were used to monitor ATP alterations in H+ fluxes from isolated Müller cells of tiger salamander, human and other species. ATP-induced alterations in extracellular H+ were also examined in tiger salamander retinal slices with self referencing H+-sensitive electrodes and in intact transgenic zebrafish retinae expressing the extracellular pH reporter CalipHluorin on the external surface of photoreceptor synaptic terminals.

Results : Micromolar concentrations of extracellular ATP induced a pronounced increase in extracellular H+ flux from Müller cells isolated from tiger salamander that was mimicked by ADP, UTP and ATPγs and was significantly reduced by the ATP receptor inhibitors suramin and PPADS. Bath-applied ATP induced an intracellular rise in calcium in Müller cells; both the calcium rise and the extracellular H+ fluxes were significantly attenuated when calcium re-loading into the endoplasmic reticulum was inhibited by the calcium uptake inhibitor thapsigargin and when the PLC-IP3 signaling pathway was disrupted with the inhibitors 2-APB and U73122. Extracellular ATP also induced large extracellular H+ fluxes from Müller cells isolated from human retinae and several other species. Large ATP-induced increases in extracellular H+ fluxes were also observed when self-referencing H+ electrodes were placed at the level of the outer plexiform layer of slices of tiger salamander retina; the H+ flux increases were significantly reduced by the ATP receptor blockers PPADS and suramin. ATP-induced extracellular acidifications were also detected by the extracellular pH reporter CalipHluorin expressed on the external surface of photoreceptor synaptic terminals in whole mount zebrafish retinae.

Conclusions : Given the high sensitivity of voltage-gated calcium channels on photoreceptors and other retinal neurons to small changes in extracellular pH, our data suggest that ATP-induced modulation of extracellular H+ levels by Müller cells may play a key role in regulating neurotransmitter release by retinal neurons.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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