ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
The contribution of resurgent sodium current to high-frequency firing in Purkinje neurons: an experimental and modeling study.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
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199 citing papers in PubMed, 327 citations in OpenAlex.
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- A Reinterpretation of the Relationship between Persistent and Resurgent Sodium Currents.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Resurgent current in context: Insights from the structure and function of Na and K channels.Biophysical journal · 2024Review
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139 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Purkinje neurons generate high-frequency action potentials and express voltage-gated, tetrodotoxin-sensitive sodium channels with distinctive kinetics. Their sodium currents activate and inactivate during depolarization, as well as reactivate during repolarization from positive potentials, producing a "resurgent" current. This reopening of channels not only generates inward current after each action potential, but also permits rapid recovery from inactivation, leading to the hypothesis that resurgent current may facilitate high-frequency firing. Mutant med mice are ataxic and lack expression of the Scn8a gene, which encodes the NaV1.6 protein. In med Purkinje cells, transient sodium current inactivates more rapidly than in wild-type cells, and resurgent current is nearly abolished. To investigate how NaV1.6-specific kinetics influence firing patterns, we recorded action potentials of Purkinje neurons isolated from wild-type and med mice. We also recorded non-sodium currents from Purkinje cells of both genotypes to test whether the Scn8a mutation induced changes in other ion channels. Last, we modeled action potential firing by simulating eight currents directly recorded from Purkinje cells in both wild-type and med mice. Regular, high-frequency firing was slowed in med Purkinje neurons. In addition to disrupted sodium currents, med neurons had small but significant changes in potassium and leak currents. Simulations indicated that these modified non-sodium currents could not account for the reduced excitability of med cells but instead slightly facilitated spiking. The loss of NaV1.6-specific kinetics, however, slowed simulated spontaneous activity. Together, the data suggest that across a range of conditions, sodium currents with a resurgent component promote and accelerate firing.
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12832512PMC6741194W2118279723What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.