Sources of protons and a role for bicarbonate in inhibitory feedback from horizontal cells to cones in Ambystoma tigrinum retina

Key points In the vertebrate retina, photoreceptors influence the signalling of neighbouring photoreceptors through lateral‐inhibitory interactions mediated by horizontal cells (HCs). These interactions create antagonistic centre‐surround receptive fields important for detecting edges and generating...

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Bibliographic Details
Published in:The Journal of physiology 2016-11, Vol.594 (22), p.6661-6677
Main Authors: Warren, Ted J., Hook, Matthew J., Supuran, Claudiu T., Thoreson, Wallace B.
Format: Article
Language:English
Subjects:
Ambystoma - metabolism
Ambystoma tigrinum
Animals
Bicarbonates - metabolism
Calcium - metabolism
calcium current
Caudata
Cellular and Molecular Neuroscience
Feedback
horizontal cell
Hydrogen-Ion Concentration
Light
Membrane Potentials - physiology
Neuroscience ‐ Cellular/Molecular
Patch-Clamp Techniques - methods
pH regulation
Photic Stimulation - methods
photoreceptor
Protons
Research Paper
retina
Retina - metabolism
Retinal Cone Photoreceptor Cells - metabolism
Retinal Horizontal Cells - metabolism
Synapses - metabolism
Urodela - metabolism
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Summary:Key points In the vertebrate retina, photoreceptors influence the signalling of neighbouring photoreceptors through lateral‐inhibitory interactions mediated by horizontal cells (HCs). These interactions create antagonistic centre‐surround receptive fields important for detecting edges and generating chromatically opponent responses in colour vision. The mechanisms responsible for inhibitory feedback from HCs involve changes in synaptic cleft pH that modulate photoreceptor calcium currents. However, the sources of synaptic protons involved in feedback and the mechanisms for their removal from the cleft when HCs hyperpolarize to light remain unknown. Our results indicate that Na+–H+ exchangers are the principal source of synaptic cleft protons involved in HC feedback but that synaptic cleft alkalization during light‐evoked hyperpolarization of HCs also involves changes in bicarbonate transport across the HC membrane. In addition to delineating processes that establish lateral inhibition in the retina, these results contribute to other evidence showing the key role for pH in regulating synaptic signalling throughout the nervous system. Lateral‐inhibitory feedback from horizontal cells (HCs) to photoreceptors involves changes in synaptic cleft pH accompanying light‐evoked changes in HC membrane potential. We analysed HC to cone feedback by studying surround‐evoked light responses of cones and by obtaining paired whole cell recordings from cones and HCs in salamander retina. We tested three potential sources for synaptic cleft protons: (1) generation by extracellular carbonic anhydrase (CA), (2) release from acidic synaptic vesicles and (3) Na+/H+ exchangers (NHEs). Neither antagonizing extracellular CA nor blocking loading of protons into synaptic vesicles eliminated feedback. However, feedback was eliminated when extracellular Na+ was replaced with choline and significantly reduced by an NHE inhibitor, cariporide. Depriving NHEs of intracellular protons by buffering HC cytosol with a pH 9.2 pipette solution eliminated feedback, whereas alkalinizing the cone cytosol did not, suggesting that HCs are a major source for protons in feedback. We also examined mechanisms for changing synaptic cleft pH in response to changes in HC membrane potential. Increasing the trans‐membrane proton gradient by lowering the extracellular pH from 7.8 to 7.4 to 7.1 strengthened feedback. While maintaining constant extracellular pH with 1 mm HEPES, removal of bicarbonate abolished f
ISSN:0022-3751
1469-7793
DOI:10.1113/JP272533