Chondroitin Sulfates Act as Extracellular Gating Modifiers on Voltage-Dependent Ion Channels
Open accessAbstract
BACKGROUND/AIMS: Chondroitin sulfates are glycosaminoglycans bound to core proteins of proteoglycans in the extracellular matrix and perineuronal nets surrounding many types of neurones. Chondroitin 4- and chondroitin 6- sulfate can bind calcium ions with different affinities, depending on their sulfation position. Extracellular calcium plays a key role in determining the transmembrane potential sensed by voltage-operated ion channels (VOCs) by means of the "surface screening effect" theory (Gouy-Chapman-Stern theory). We wanted to test whether chondroitin sulfates at physiological concentration can effectively modulate the gating properties of VOCs. METHODS: We recorded in patch-clamp experiments the shift of h and voltage-dependent calcium currents activation curves of Xenopus laevis photoreceptors perfused with chondroitin sulfate solutions in physiological extracellular calcium concentration. RESULTS: We found that chondroitin 4- and 6- sulfate, with different capabilities, can shift the activation curve of h and voltage-dependent calcium channels, compatibly with the surface screening effect theory. CONCLUSION: We conclude that chondroitin sulfates can alter VOCs gating by modulating the calcium concentration in the extracellular microenvironment. This phenomenon may explain why alterations in the chondroitin sulfation and abundance in the extracellular matrix are found along with altered neuronal function in pathological conditions.
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The role of CSPGs in PNN functions depends, at least in part, on their sulfation pattern; for instance CS-6 and CS-4 impact voltage-dependent calcium channels in distinct ways.
“Relevant to the present results, the role of CSPGs in these functions depends, at least in part, on their sulfation pattern; for instance CS-6 and CS-4 impact voltage-dependent calcium channels in distinct ways.89”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [89]
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- Authors
- Vigetti, D., Andrini, O., Clerici, M., Negrini, D., Passi, A., & Moriondo, A.
- Affiliations
- University of Insubria (IT)
- Venue
- Cellular Physiology and Biochemistry
- Publisher
- S. Karger AG
- Published
- 2008
- Volume
- 22
- Issue
- 1-4
- Pages
- 137-146
- ISSN
- 1015-8987 (ISSN-L)
- 1421-9778
- OpenAlex
- W2013271982
- Cited by
- 38
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 2 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 1 · 2012: 3
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cellular Physiology and Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- IrInSubria (University of Insubria) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- 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
- Keywords
- chondroitin sulfate, chondroitin 4-sulfate, chondroitin-6-sulfate, voltage-gated ion channels, channel gating, Gouy-Chapman-Stern theory, extracellular calcium, H+ channel, voltage-gated calcium channels, photoreceptors, extracellular matrix, glycosaminoglycans, sulfation
- MeSH terms
- Animals, Calcium, Chondroitin Sulfates, Electrophoresis, Polyacrylamide Gel, Extracellular Space, Ion Channels, Xenopus, Calcium Channels, Ion Channel Gating
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