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Altered Subthreshold Sodium Currents and Disrupted Firing Patterns in Purkinje Neurons of Scn8a Mutant Mice
Open accessAbstract
Sodium currents and action potentials were characterized in Purkinje neurons from ataxic mice lacking expression of the sodium channel Scn8a. Peak transient sodium current was approximately 60% of that in normal mice, but subthreshold sodium current was affected much more. Steady-state current elicited by voltage ramps was reduced to approximately 30%, and resurgent sodium current, an unusual transient current elicited on repolarization following strong depolarizations, was reduced to 8%-18%. In jolting mice, with a missense mutation in Scn8a, steady-state and resurgent current were also reduced, with altered voltage dependence and kinetics. Both spontaneous firing and evoked bursts of spikes were diminished in cells from null and jolting mice. Evidently Scn8a channels carry most subthreshold sodium current and are crucial for repetitive firing.
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“The pace-making defect in the L7-DKO mice is highly reminiscent of mice lacking the voltage-gated sodium channel subunit Scn8a (REFS 141–143).”
From The neurogenetics of alternative splicing (2016) · cites this paper as [141]
In the citing paper
“Nav1.6 functions, in part, to maintain a resurgent sodium current that enables regular, spontaneous firing.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [141]
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Social Deficits and Cerebellar Degeneration in Purkinje Cell Scn8a Knockout Mice
Yang, X., Yin, H., Wang, X., Sun, Y., Bian, X., Zhang, G., Li, A., Cao, A., Li, B., Ebrahimi‐Fakhari, D., et al. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.822129 · Cited by 10
Self-citation
Metadata
- Authors
- Raman, I. M., Sprunger, L. K., Meisler, M. H., & Bean, B. P.
- Affiliations
- Harvard University (US)
- University of Michigan (US)
- Corresponding author
- Raman, Indira M
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 19
- Issue
- 4
- Pages
- 881-891
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2090477486
- Cited by
- 390
- References
- 45
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 14 · 2022: 14 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 11 · 2017: 16 · 2016: 14 · 2015: 11 · 2014: 14 · 2013: 10 · 2012: 21
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS036855, F32-NS10396, R01-NS34059, R01NS36855, F32NS010396)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- SCN8A, sodium channels, Purkinje cells, resurgent sodium current, missense mutations, ataxia, repetitive firing, action potential, cerebellum
- MeSH terms
- Animals, Calcium, Crosses, Genetic, Evoked Potentials, Genotype, Heterozygote, Kinetics, Membrane Potentials, Mice, Inbred C3H, Mice, Inbred C57BL, Nerve Tissue Proteins, Purkinje Cells, Time Factors, Sodium Channels, Polymerase Chain Reaction, Mice, Knockout, Patch-Clamp Techniques, Mice, NAV1.6 Voltage-Gated Sodium Channel, In Vitro Techniques
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