ArticleFrontiers in cellular neuroscience2014
Molecular identity of axonal sodium channels in human cortical pyramidal cells.
Article in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Neuroanatomical and psychological considerations in temporal lobe epilepsy.Frontiers in neuroanatomy · 2022Pooled it
- Nanoscale organization in the cell membrane dynamically modulates the biophysics of voltage-gated sodium channels.Nature communications · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Distribution of Voltage-Gated Sodium Channels and Scaffolding Proteins on Vestibular Calyx Ending Delineates the Axon Initial Segment.The Journal of comparative neurology · 2026Article
- Neurologist's Black Swan: Molecular Basis of Prenatal Seizures.International journal of molecular sciences · 2025Review
- Optic nerve injury impairs intrinsic mechanisms underlying electrical activity in a resilient retinal ganglion cell.The Journal of physiology · 2025Article
- FGF14 Peptide Derivative Differentially Regulates Nav1.2 and NaLife (Basel, Switzerland) · 2025Article
- Differential roles of NaeLife · 2025Article
- Axon initial segment structure and function in health and disease.Physiological reviews · 2025Review
- Generation and characterization of human-induced pluripotent stem cell lines from patients with autism spectrum disorder and SCN2A variants.Human cell · 2025Article
- Restoration of excitation/inhibition balance enhances neuronal signal-to-noise ratio and rescues social deficits in autism-associatedbioRxiv : the preprint server for biology · 2025Article
- Specific and Plastic: Chandelier Cell-to-Axon Initial Segment Connections in Shaping Functional Cortical Network.Neuroscience bulletin · 2024Review
- Schwann cell-secreted PGECell · 2024Article
- Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally.Science advances · 2024Article
- Shining a Light on Venom-Peptide Receptors: Venom Peptides as Targeted Agents for In Vivo Molecular Imaging.Toxins · 2024Review
- Pathogenic gating pore current conducted by autism-related mutations in the NaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Impact on backpropagation of the spatial heterogeneity of sodium channel kinetics in the axon initial segment.PLoS computational biology · 2024Article
- Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-FunctionThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Variation and convergence in the morpho-functional properties of the mammalian neocortex.Frontiers in systems neuroscience · 2024Review
- Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies in rodents revealed that selective accumulation of Na(+) channel subtypes at the axon initial segment (AIS) determines action potential (AP) initiation and backpropagation in cortical pyramidal cells (PCs); however, in human cortex, the molecular identity of Na(+) channels distributed at PC axons, including the AIS and the nodes of Ranvier, remains unclear. We performed immunostaining experiments in human cortical tissues removed surgically to cure brain diseases. We found strong immunosignals of Na(+) channels and two channel subtypes, NaV1.2 and NaV1.6, at the AIS of human cortical PCs. Although both channel subtypes were expressed along the entire AIS, the peak immunosignals of NaV1.2 and NaV1.6 were found at proximal and distal AIS regions, respectively. Surprisingly, in addition to the presence of NaV1.6 at the nodes of Ranvier, NaV1.2 was also found in a subpopulation of nodes in the adult human cortex, different from the absence of NaV1.2 in myelinated axons in rodents. NaV1.1 immunosignals were not detected at either the AIS or the nodes of Ranvier of PCs; however, they were expressed at interneuron axons with different distribution patterns. Further experiments revealed that parvalbumin-positive GABAergic axon cartridges selectively innervated distal AIS regions with relatively high immunosignals of NaV1.6 but not the proximal NaV1.2-enriched compartments, suggesting an important role of axo-axonic cells in regulating AP initiation in human PCs. Together, our results show that both NaV1.2 and NaV1.6 (but not NaV1.1) channel subtypes are expressed at the AIS and the nodes of Ranvier in adult human cortical PCs, suggesting that these channel subtypes control neuronal excitability and signal conduction in PC axons.
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