Cited by 390Ion channel regulation and functionCardiac electrophysiology and arrhythmiasIon Transport and Channel Regulation

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Altered Subthreshold Sodium Currents and Disrupted Firing Patterns in Purkinje Neurons of Scn8a Mutant Mice

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Raman, Indira M, Sprunger, Leslie K, Meisler, Miriam H, Bean, Bruce P·1997·Neuron

DOI 10.1016/s0896-6273(00)80969-1

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Abstract

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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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
ORCID: Raman, Indira M
Meisler, Miriam H
Bean, Bruce P
Venue: Neuron
Publisher: Elsevier BV
Published: 1997-10
Volume: 19
Issue: 4
Pages: 881-891
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/s0896-6273(00)80969-1
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5768 d)
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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Altered Subthreshold Sodium Currents and Disrupted Firing Patterns in Purkinje Neurons of Scn8a Mutant Mice

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