ATP-mediated increase in H ⁺ efflux from retinal Müller cells of the axolotl.

Publisher: American Physiological Society Country of Publication: United States NLM ID: 0375404 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1598 (Electronic) Linking ISSN: 00223077 NLM ISO Abbreviation: J Neurophysiol Subsets: MEDLINE

Publication: Bethesda Md : American Physiological Society
Original Publication: Washington [etc.]

Ependymoglial Cells*/metabolism ; Ambystoma mexicanum*/metabolism; Animals ; Calmodulin/metabolism ; Calcium/metabolism ; Amiloride/metabolism ; Adenosine Triphosphate/metabolism ; Neuroglia/metabolism ; Retina

Previous work has shown that activation of tiger salamander retinal radial glial cells by extracellular ATP induces a pronounced extracellular acidification, which has been proposed to be a potent modulator of neurotransmitter release. This study demonstrates that low micromolar concentrations of extracellular ATP similarly induce significant H ⁺ effluxes from Müller cells isolated from the axolotl retina. Müller cells were enzymatically isolated from axolotl retina and H ⁺ fluxes were measured from individual cells using self-referencing H ⁺ -selective microelectrodes. The increased H ⁺ efflux from axolotl Müller cells induced by extracellular ATP required activation of metabotropic purinergic receptors and was dependent upon calcium released from internal stores. We further found that the ATP-evoked increase in H ⁺ efflux from Müller cells of both tiger salamander and axolotl were sensitive to pharmacological agents known to interrupt calmodulin and protein kinase C (PKC) activity: chlorpromazine (CLP), trifluoperazine (TFP), and W-7 (all calmodulin inhibitors) and chelerythrine, a PKC inhibitor, all attenuated ATP-elicited increases in H ⁺ efflux. ATP-initiated H ⁺ fluxes of axolotl Müller cells were also significantly reduced by amiloride, suggesting a significant contribution by sodium-hydrogen exchangers (NHEs). In addition, α-cyano-4-hydroxycinnamate (4-cin), a monocarboxylate transport (MCT) inhibitor, also reduced the ATP-induced increase in H ⁺ efflux in both axolotl and tiger salamander Müller cells, and when combined with amiloride, abolished ATP-evoked increase in H ⁺ efflux. These data suggest that axolotl Müller cells are likely to be an excellent model system to understand the cell-signaling pathways regulating H ⁺ release from glia and the role this may play in modulating neuronal signaling. NEW & NOTEWORTHY Glial cells are a key structural part of the tripartite synapse and have been suggested to regulate synaptic transmission, but the regulatory mechanisms remain unclear. We show that extracellular ATP, a potent glial cell activator, induces H ⁺ efflux from axolotl retinal Müller (glial) cells through a calcium-dependent pathway that is likely to involve calmodulin, PKC, Na ⁺ /H ⁺ exchange, and monocarboxylate transport, and suggest that such H ⁺ release may play a key role in modulating neuronal transmission.

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1557725 National Science Foundation (NSF); UL1TR002003 UIC CCTS NIH; UL1 TR002003 United States TR NCATS NIH HHS; 1557820 National Science Foundation (NSF); Indiana Wesleyan University University Scholar award; UICenter for Drug Development grant; Indiana Wesleyan University Hodson Research Institute award; P40 OD019794 United States OD NIH HHS

Keywords: calmodulin; glia; monocarboxylate transport; pH; protein kinase C

0 (Calmodulin)
SY7Q814VUP (Calcium)
7DZO8EB0Z3 (Amiloride)
8L70Q75FXE (Adenosine Triphosphate)

Date Created: 20231220 Date Completed: 20240117 Latest Revision: 20240828

20240828

PMC11286307

10.1152/jn.00321.2023

38116604