Zn 2+ currents are mediated by calcium‐permeable AMPA/Kainate channels in cultured murine hippocampal neurones
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Permeation of the endogenous cation Zn 2+ through calcium‐permeable AMPA/kainate receptor‐gated (Ca‐A/K) channels might subserve pathological and/or physiological signalling roles. Voltage‐clamp recording was used to directly assess Zn 2+ flux through these channels on cultured murine hippocampal neurones. Ca‐A/K channels were present in large numbers only on a minority of neurones (Ca‐A/K(+) neurones), many of which were GABAergic. The presence of these channels was assessed in whole‐cell or outside‐out patch recording as the degree of inward rectification of kainate‐activated currents, quantified via a rectification index (RI = G +40 / G ‐ 60 ), which ranged from <0.4 (strongly inwardly rectifying) to >2 (outwardly rectifying). The specificity of a low RI as an indication of robust Ca‐A/K channel expression was verified by two other techniques, kainate‐stimulated cobalt‐uptake labelling, and fluorescence imaging of kainate‐induced increases in intracellular Ca 2+ . In addition, the degree of inward rectification of kainate‐activated currents correlated strongly with the positive shift of the reversal potential ( V rev ) upon switching to a sodium‐free, 10 m m Ca 2+ buffer. With Zn 2+ (3 m m ) as the only permeant extracellular cation, kainate‐induced inward currents were only observed in neurones that had previously been identified as Ca‐A/K(+). A comparison between the V rev observed with 3 m m Zn 2+ and that observed with Ca 2+ as the permeant cation revealed a P Ca / P Zn of ≈1.8. Inward currents recorded in 3 m m Ca 2+ were unaffected by the addition of 0.3 m m Zn 2+ , while microfluorimetrically detected increases in the intracellular concentration of Zn 2+ in Ca‐A/K(+) neurones upon kainate exposure in the presence of 0.3 m m Zn 2+ were only mildly attenuated by the addition of 1.8 m m Ca 2+ . These results provide direct evidence that Zn 2+ can carry currents through Ca‐A/K channels, and that there is little interference between Ca 2+ and Zn 2+ in permeating these channels.
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Calcium-permeable AMPA receptors are a major entry point for zinc.
“Ca 2+ -permeable AMPA receptors are a major entry point of zinc [111-113].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [113]
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- Authors
- Jia, Y., Jeng, J., Sensi, S. L., & Weiss, J. H.
- Affiliations
- University of California, Irvine (US)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2002-08
- Volume
- 543
- Issue
- 1
- Pages
- 35-48
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2290471
- OpenAlex
- W2070802660
- Cited by
- 118
- References
- 61
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 6 · 2014: 3 · 2013: 2 · 2012: 7
- FWCI
- 1.98
- 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 Institutes of Health (5k02ag000836-05, 5r01ns030884-11)
- University of California, Irvine
- National Institute on Aging (AG00836, AG 00919, K01AG000919)
- National Institute of Neurological Disorders and Stroke (NS 30884)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- kainate receptors, inward rectification, reversal potential, GABAergic neurons, hippocampal neurons, intracellular zinc, calcium permeation
- MeSH terms
- Animals, Calcium, Cells, Cultured, Drug Interactions, Female, Hippocampus, Membrane Potentials, Neurons, Pregnancy, Zinc, Ion Channel Gating, Receptors, AMPA, Kainic Acid Receptors, Receptors, Kainic Acid, Patch-Clamp Techniques, Mice
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