Hemichannel-mediated and pH-based feedback from horizontal cells to cones in the vertebrate retina
Autor: | I. Fahrenfort, R. Numan, Trijntje Sjoerdsma, MN Marvin Steijaert, Evan Vickers, Jan Klooster, Duco Endeman, Harris Ripps, Maarten Kamermans, Jorrit B. van Asselt, Huub M. M. ten Eikelder, Henrique von Gersdorff |
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Přispěvatelé: | Other departments, Biomedical Engineering and Physics, Amsterdam Neuroscience, Netherlands Institute for Neuroscience (NIN), Computational Biology |
Jazyk: | angličtina |
Rok vydání: | 2009 |
Předmět: |
Biophysics/Theory and Simulation
Synaptic cleft Ephaptic coupling lcsh:Medicine Acetates Neurotransmission Models Biological Synaptic Transmission Retina Xenopus laevis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Goldfish Neuroscience/Neuronal Signaling Mechanisms Extracellular medicine Animals lcsh:Science 030304 developmental biology Feedback Physiological HEPES Membrane potential 0303 health sciences Multidisciplinary Chemistry Neuroscience/Sensory Systems lcsh:R Anatomy Hydrogen-Ion Concentration Hyperpolarization (biology) Electrophysiology medicine.anatomical_structure Vertebrates Oocytes Retinal Cone Photoreceptor Cells Biophysics Calcium Female lcsh:Q sense organs 030217 neurology & neurosurgery Research Article |
Zdroj: | PLoS ONE, Vol 4, Iss 6, p e6090 (2009) PLoS ONE, 4(6). Public Library of Science PLoS One, 4. Public Library of Science PLoS ONE, 4(6):e6090. Public Library of Science PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Background: Recent studies designed to identify the mechanism by which retinal horizontal cells communicate with cones have implicated two processes. According to one account, horizontal cell hyperpolarization induces an increase in pH within the synaptic cleft that activates the calcium current (Ca 2+ -current) in cones, enhancing transmitter release. An alternative account suggests that horizontal cell hyperpolarization increases the Ca 2+ -current to promote transmitter release through a hemichannel-mediated ephaptic mechanism. Methodology/Principal Findings: To distinguish between these mechanisms, we interfered with the pH regulating systems in the retina and studied the effects on the feedback responses of cones and horizontal cells. We found that the pH buffers HEPES and Tris partially inhibit feedback responses in cones and horizontal cells and lead to intracellular acidification of neurons. Application of 25 mM acetate, which does not change the extracellular pH buffer capacity, does lead to both intracellular acidification and inhibition of feedback. Because intracellular acidification is known to inhibit hemichannels, the key experiment used to test the pH hypothesis, i.e. increasing the extracellular pH buffer capacity, does not discriminate between a pH-based feedback system and a hemichannel-mediated feedback system. To test the pH hypothesis in a manner independent of artificial pH-buffer systems, we studied the effect of interfering with the endogenous pH buffer, the bicarbonate/carbonic anhydrase system. Inhibition of carbonic anhydrase allowed for large changes in pH in the synaptic cleft of bipolar cell terminals and cone terminals, but the predicted enhancement of the cone feedback responses, according to the pH-hypothesis, was not observed. These experiments thus failed to support a proton mediated feedback mechanism. The alternative hypothesis, the hemichannel-mediated ephaptic feedback mechanism, was therefore studied experimentally, and its feasibility was buttressed by means of a quantitative computer model of the cone/horizontal cell synapse. Conclusion: We conclude that the data presented in this paper offers further support for physiologically relevant ephaptic interactions in the retina. |
Databáze: | OpenAIRE |
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