Calcium diffusion enhanced after cleavage of negatively charged components of brain extracellular matrix by chondroitinase ABC
Open accessAbstract
The concentration of extracellular calcium plays a critical role in synaptic transmission and neuronal excitability as well as other physiological processes. The time course and extent of local fluctuations in the concentration of this ion largely depend on its effective diffusion coefficient (D*) and it has been speculated that fixed negative charges on chondroitin sulphate proteoglycans (CSPGs) and other components of the extracellular matrix may influence calcium diffusion because it is a divalent cation. In this study we used ion‐selective microelectrodes combined with pressure ejection or iontophoresis of ions from a micropipette to quantify diffusion characteristics of neocortex and hippocampus in rat brain slices. We show that D* for calcium is less than the value predicted from the behaviour of the monovalent cation tetramethylammonium (TMA), a commonly used diffusion probe, but D* for calcium increases in both brain regions after the slices are treated with chondroitinase ABC, an enzyme that predominantly cleaves chondroitin sulphate glycans. These results suggest that CSPGs do play a role in determining the local diffusion properties of calcium in brain tissue, most likely through electrostatic interactions mediating rapid equilibrium binding. In contrast, chondroitinase ABC does not affect either the TMA diffusion or the extracellular volume fraction, indicating that the enzyme does not alter the structure of the extracellular space and that the diffusion of small monovalent cations is not affected by CSPGs in the normal brain ionic milieu. Both calcium and CSPGs are known to have many distinct roles in brain physiology, including brain repair, and our study suggests they may be functionally coupled through calcium diffusion properties.
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A facilitated diffusion of dissociated FeCl3 due to the lack of PN components most likely accounts for the increased spreading of degeneration in knockout mice.
“On the background of previous reports on the contribution of lecticans40, 41 and TN-R42 to the diffusion and hydration properties of the neural ECM, a facilitated diffusion of dissociated FeCl3 due to the lack of PN components most likely accounts for these effects.”
From Aggrecan, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress (2014) · cites this paper as [41]
Others have suggested altered lateral mobility of AMPAR or changes in local diffusion of Ca2+ in brain tissue following PNN degradation.
“Others have suggested altered lateral mobility of AMPAR53 or changes in the local diffusion of Ca2+ in brain tissue54 following PNN degradation.”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [54]
Enhanced calcium diffusion within brain tissue influences synaptic transmission, neuronal excitability and other physiological processes.
“Notably, the ChABC-induced removal of negatively charged ECM components such as glycosaminoglycans resulted in enhanced calcium diffusion within brain tissue which influences synaptic transmission, neuronal excitability and other physiological processes (Hrabětová et al., 2009).”
From Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep (2017) · cites this paper as Hrabětová et al., 2009
ChABC-induced removal of negatively charged extracellular matrix components such as glycosaminoglycans resulted in enhanced calcium diffusion within brain tissue.
“Notably, the ChABC-induced removal of negatively charged ECM components such as glycosaminoglycans resulted in enhanced calcium diffusion within brain tissue which influences synaptic transmission, neuronal excitability and other physiological processes (Hrabětová et al., 2009).”
From Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep (2017) · cites this paper as Hrabětová et al., 2009
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- Authors
- Hrabětová, S., Masri, D., Tao, L., Xiao, F., & Nicholson, C.
- Affiliations
- SUNY Downstate Health Sciences University (US)
- New York University (US)
- Corresponding author
- Nicholson, Charles
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2009-08-14
- Volume
- 587
- Issue
- 16
- Pages
- 4029-4049
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2756436
- OpenAlex
- W1500029814
- Cited by
- 113
- References
- 79
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 6 · 2023: 4 · 2022: 2 · 2021: 10 · 2020: 8 · 2019: 3 · 2018: 12 · 2017: 8 · 2016: 6 · 2015: 11 · 2014: 5 · 2013: 11 · 2012: 6
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS028642, R01NS028642, R56NS047557, NS047557, R01NS047557)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- calcium diffusion, extracellular matrix, chondroitin sulfate proteoglycans, chondroitinase ABC, negative charge, electrostatic interactions, tetramethylammonium, extracellular volume fraction, neocortex, hippocampus, ion-selective microelectrodes, iontophoresis, brain repair
- MeSH terms
- Animals, Brain, Brain Chemistry, Calcium, Diffusion, Dose-Response Relationship, Drug, Extracellular Matrix, Female, Rats, Sprague-Dawley, Chondroitin ABC Lyase, Rats, Static Electricity
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