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Resurgent Sodium Current and Action Potential Formation in Dissociated Cerebellar Purkinje Neurons
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Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje neurons from rats. In whole-cell recordings, a tetrodotoxin (TTX)-sensitive inward current was elicited when the membrane was repolarized to voltages between −60 and −20 mV after depolarizations to +30 mV long enough to produce maximal inactivation. At −40 mV, this “resurgent” current peaked in 8 msec and decayed with a time constant of 30 msec. With 50 m m sodium as a charge carrier, the resurgent current was on average ∼120 pA. CA3 pyramidal neurons had no such current. The current may reflect recovery of inactivated channels through open states, because in Purkinje neurons (but not CA3 neurons) there was partial recovery from inactivation at −40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels gave openings corresponding to resurgent and conventional transient current. Action potentials were recorded from dissociated neurons under current clamp to investigate the role of the resurgent current in action potential formation. Purkinje neurons fired spontaneously at ∼30 Hz. Hyperpolarization to −85 mV prevented spontaneous firing, and brief depolarization then induced all-or-none firing of conglomerate action potentials comprising three to four spikes. When conglomerate action potentials were used as command voltages in voltage-clamp experiments, TTX-sensitive sodium current was elicited between spikes. The falling phase of an action potential is similar to voltage patterns that activate resurgent sodium current, and thus, resurgent sodium current likely contributes to the formation of conglomerate action potentials in Purkinje neurons.
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“Several alternatively spliced exons in Scn8a contribute to the resurgent sodium current144,145.”
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Metadata
- Authors
- Raman, I. M., & Bean, B. P.
- Affiliations
- Harvard University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-06-15
- Volume
- 17
- Issue
- 12
- Pages
- 4517-4526
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6573347
- OpenAlex
- W1537888364
- Cited by
- 568
- References
- 27
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 19 · 2023: 15 · 2022: 13 · 2021: 22 · 2020: 23 · 2019: 29 · 2018: 22 · 2017: 19 · 2016: 37 · 2015: 21 · 2014: 30 · 2013: 16 · 2012: 33
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl035034-19, HL 35034)
- National Heart, Lung, and Blood Institute (HL 35034)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- resurgent sodium current, voltage-gated sodium channels, Purkinje cells, tetrodotoxin-sensitive sodium current, CA3 pyramidal cells, spontaneous firing, single-channel recording
- MeSH terms
- Action Potentials, Animals, Cell Adhesion, Evoked Potentials, Hippocampus, Purkinje Cells, Tetrodotoxin, Time Factors, Sodium Channels, Pyramidal Cells, Patch-Clamp Techniques, Rats, In Vitro Techniques
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