Activation of retinal glial (Müller) cells by extracellular ATP induces pronounced increases in extracellular H+ flux
| Autor: | Michael Gongwer, Robert Paul Malchow, Boriana K. Tchernookova, Matthew A. Kreitzer, Jason Jacoby, David Swygart, Lexi Shepherd, Ryan Kaufman, Marin Young, Hannah Caringal, Chad Heer |
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| Rok vydání: | 2022 |
| Předmět: |
0301 basic medicine
Photoreceptors P2Y receptor Caudata Sensory Receptors lcsh:Medicine Social Sciences 4 4'-Diisothiocyanostilbene-2 2'-Disulfonic Acid Ambystoma Biochemistry chemistry.chemical_compound 0302 clinical medicine Adenosine Triphosphate Cell Signaling Animal Cells Medicine and Health Sciences Psychology Skates Fish lcsh:Science Uncategorized Neurons Multidisciplinary Physics Lampreys Eukaryota Neurochemistry Neurotransmitters Hydrogen-Ion Concentration Adenosine Diphosphate Chemistry Pyridoxal Phosphate Receptors Purinergic P2Y Physical Sciences Vertebrates Engineering and Technology Sensory Perception Signal transduction Anatomy Cellular Types Glutamate Protons Intracellular Signal Transduction Research Article Thapsigargin Ocular Anatomy Ependymoglial Cells Suramin In Vitro Techniques Retina Amphibians 03 medical and health sciences Ocular System Extracellular Animals Humans PPADS Calcium Signaling Salamanders Electrodes Ion transporter Nuclear Physics Nucleons Ion Transport lcsh:R Chemical Compounds Organisms Bicarbonate transport Biology and Life Sciences Afferent Neurons Extracellular Fluid Cell Biology Macaca mulatta Rats Ictaluridae Macaca fascicularis Bicarbonates 030104 developmental biology chemistry Cellular Neuroscience Biophysics lcsh:Q sense organs Electronics Microelectrodes 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 2, p e0190893 (2018) |
| DOI: | 10.25417/uic.19491584.v1 |
| Popis: | Small alterations in extracellular acidity are potentially important modulators of neuronal signaling within the vertebrate retina. Here we report a novel extracellular acidification mechanism mediated by glial cells in the retina. Using self-referencing H+-selective microelectrodes to measure extracellular H+ fluxes, we show that activation of retinal Müller (glial) cells of the tiger salamander by micromolar concentrations of extracellular ATP induces a pronounced extracellular H+ flux independent of bicarbonate transport. ADP, UTP and the non-hydrolyzable analog ATPγs at micromolar concentrations were also potent stimulators of extracellular H+ fluxes, but adenosine was not. The extracellular H+ fluxes induced by ATP were mimicked by the P2Y1 agonist MRS 2365 and were significantly reduced by the P2 receptor blockers suramin and PPADS, suggesting activation of P2Y receptors. 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 thapsigargin and when the PLC-IP3 signaling pathway was disrupted with 2-APB and U73122. The anion transport inhibitor DIDS also markedly reduced the ATP-induced increase in H+ flux while SITS had no effect. ATP-induced H+ fluxes were also observed from Müller cells isolated from human, rat, monkey, skate and lamprey retinae, suggesting a highly evolutionarily conserved mechanism of potential general importance. Extracellular ATP also induced significant increases in extracellular H+ flux at the level of both the outer and inner plexiform layers in retinal slices of tiger salamander which was significantly reduced by suramin and PPADS. We suggest that the novel H+ flux mediated by ATP-activation of Müller cells and of other glia as well may be a key mechanism modulating neuronal signaling in the vertebrate retina and throughout the brain. |
| Databáze: | OpenAIRE |
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