ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Cross-species conservation of open-channel block by Na channel β4 peptides reveals structural features required for resurgent Na current.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons.Molecular pain · 2012Trial
- Resurgent current in context: Insights from the structure and function of Na and K channels.Biophysical journal · 2024Review
- Molecular determinants of resurgent sodium currents mediated by Navβ4 peptide and A-type FHFs.Frontiers in molecular neuroscience · 2024Article
- Characterization of NaLife science alliance · 2024Article
- The Hodgkin-Huxley-Katz Prize Lecture: A Markov model with permeation-dependent gating that accounts for resurgent current of voltage-gated Na channels.The Journal of physiology · 2023Article
- A-type FHFs mediate resurgent currents through TTX-resistant voltage-gated sodium channels.eLife · 2022Article
- Resurgent NaNature communications · 2021Article
- Resurgent Sodium Current in Neurons of the Cerebral Cortex.Frontiers in cellular neuroscience · 2021Article
- Mapping of the FGF14:Nav1.6 complex interface reveals FLPK as a functionally active peptide modulating excitability.Physiological reports · 2020Article
- Effects of FGF14 and NaThe Journal of general physiology · 2019Article
- Differential Inhibition of Neuronal Sodium Channel Subtypes by the General Anesthetic Isoflurane.The Journal of pharmacology and experimental therapeutics · 2019Article
- Increased Resurgent Sodium Currents in Nav1.8 Contribute to Nociceptive Sensory Neuron Hyperexcitability Associated with Peripheral Neuropathies.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity.Cellular and molecular life sciences : CMLS · 2018Review
- Voltage-gated sodium channel β subunits: The power outside the pore in brain development and disease.Neuropharmacology · 2018Review
- Resurgent sodium current promotes action potential firing in the avian auditory brainstem.The Journal of physiology · 2018Article
- Diverse Intrinsic Properties Shape Functional Phenotype of Low-Frequency Neurons in the Auditory Brainstem.Frontiers in cellular neuroscience · 2018Article
- Need for Speed and Precision: Structural and Functional Specialization in the Cochlear Nucleus of the Avian Auditory System.Journal of experimental neuroscience · 2018Review
- Loss of Navβ4-Mediated Regulation of Sodium Currents in Adult Purkinje Neurons Disrupts Firing and Impairs Motor Coordination and Balance.Cell reports · 2017Article
- FHF2 isoforms differentially regulate Nav1.6-mediated resurgent sodium currents in dorsal root ganglion neurons.Pflugers Archiv : European journal of physiology · 2017Article
- Cardiac Na Channels: Structure to Function.Current topics in membranes · 2016Article
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2 authors.
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Abstract
Voltage-gated Na channels in many neurons, including several in the cerebellum and brainstem, are specialized to allow rapid firing of action potentials. Repetitive firing is facilitated by resurgent Na current, which flows upon repolarization as Na channels recover through open states from block by an endogenous protein. The best candidate blocking protein to date is Na(V)β4. The sequence of this protein diverges among species, however, while high-frequency firing is maintained, raising the question of whether the proposed blocking action of the Na(V)β4 cytoplasmic tail has been conserved. Here, we find that, despite differences in the Na(V)β4 sequence, Purkinje cells isolated from embryonic chick have resurgent currents with kinetics and amplitudes indistinguishable from those in mouse Purkinje cells. Furthermore, synthetic peptides derived from the divergent Na(V)β4 cytoplasmic tails from five species have the capacity to induce resurgent current in mouse hippocampal neurons, which lack a functional endogenous blocking protein. These data further support a blocking role for Na(V)β4 and also indicate the relative importance of different residues in inducing open-channel block. To investigate the contribution of the few highly conserved residues to open-channel block, we synthesized several mutant peptides in which the identities and relative orientations of a phenylalanine and two lysines were disrupted. These mutant peptides produced currents with vastly different kinetics than did the species-derived peptides, suggesting that these residues are required for an open-channel block that approximates physiological resurgent Na current. Thus, if other blocking proteins exist, they may share these structural elements with the Na(V)β4 cytoplasmic tail.
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