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Carbenoxolone Inhibition of Voltage-Gated Ca Channels and Synaptic Transmission in the Retina
Abstract
We show that carbenoxolone, a drug used to block hemichannels in the retina to test the ephaptic model of horizontal cell inhibitory feedback, has strong inhibitory effects on voltage-gated Ca channels. Carbenoxolone (100 μM) reduced photoreceptor-to-horizontal cell synaptic transmission by 92%. Applied to patch-clamped, isolated cone photoreceptors, carbenoxolone inhibited Ca channels with an EC 50 of 48 μM. At 100 μM, it reduced cone Ca channel current by 37%, reduced depolarization-evoked [Ca 2+ ] signals in fluo-4 loaded retinal slices by 57% and inhibited Ca channels in Müller cells by 52%. A synaptic transfer model suggests that the degree of block of Ca channels accounts for the reduction in synaptic transmission. These results suggest broad inhibitory actions for carbenoxolone in the retina that must be considered when interpreting its effects on inhibitory feedback.
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Metadata
- Authors
- Vessey, J. P., Lalonde, M. R., Mizan, H. A., Welch, N. C., Kelly, M. E. M., & Barnes, S.
- Affiliations
- Dalhousie University (CA)
- ORCID
- Barnes, Steven
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2004-08
- Volume
- 92
- Issue
- 2
- Pages
- 1252-1256
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W2010736218
- Cited by
- 178
- References
- 24
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 11 · 2015: 6 · 2014: 10 · 2013: 8 · 2012: 16
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- carbenoxolone, voltage-gated calcium channels, synaptic transmission, retina, horizontal cells, photoreceptors, Müller cells, hemichannels, calcium channel inhibition, cone photoreceptors
- MeSH terms
- Ambystoma, Aniline Compounds, Animals, Calcium Channel Blockers, Carbenoxolone, Electrophysiology, Fluorescent Dyes, Larva, Neural Inhibition, Synaptic Transmission, Retina, Xanthenes, Calcium Channels, Retinal Cone Photoreceptor Cells, Patch-Clamp Techniques, Photoreceptor Cells, Vertebrate, In Vitro Techniques
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