ArticleProceedings of the National Academy of Sciences of the United States of America2008
Endogenous polyamines regulate cortical neuronal excitability by blocking voltage-gated Na+ channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.Pflugers Archiv : European journal of physiology · 2024Pooled it
- Article
- ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.Nature communications · 2026Article
- Neuroinflammation leads to pharmacoresistance in temporal lobe epilepsy via promoting spermine degradation.Acta pharmacologica Sinica · 2025Article
- Article
- Intracellular Spermine Is a Key Player in GSG1L's Regulation of Calcium-Permeable AMPAR Channel Conductance and Recovery from Desensitization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Trapping of spermine, Kukoamine A, and polyamine toxin blockers in GluK2 kainate receptor channels.Nature communications · 2024Article
- Identification of SLC45A4 as a pain gene encoding a neuronal polyamine transporter.bioRxiv : the preprint server for biology · 2024Article
- Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target.Kidney diseases (Basel, Switzerland) · 2023Review
- Blockade of TRPV channels by intracellular spermine.The Journal of general physiology · 2023Article
- Repetitive transcranial magnetic stimulation enhances the neuronal excitability of mice by regulating dynamic characteristics of Granule cells' Ion channels.Cognitive neurodynamics · 2023Article
- SUMOylation of NaeLife · 2023Article
- The Potential Role of Polyamines in Epilepsy and Epilepsy-Related Pathophysiological Changes.Biomolecules · 2022Review
- Transgenic Mouse Overexpressing Spermine Oxidase in Cerebrocortical Neurons: Astrocyte Dysfunction and Susceptibility to Epileptic Seizures.Biomolecules · 2022Review
- The involvement of polyamine uptake and synthesis pathways in the proliferation of neonatal astrocytes.Amino acids · 2020Article
- Polyamine regulation of ion channel assembly and implications for nicotinic acetylcholine receptor pharmacology.Nature communications · 2020Article
- Polyamine Depletion Abrogates Enterovirus Cellular Attachment.Journal of virology · 2019Article
- THAR SHE BLOWS! The Search for the Great Spermine Whale of Carbamazepine Resistance.Epilepsy currents · 2019Article
- Bioelectrical control of positional information in development and regeneration: A review of conceptual and computational advances.Progress in biophysics and molecular biology · 2018Review
- Polyamine Modulation of Anticonvulsant Drug Response: A Potential Mechanism Contributing to Pharmacoresistance in Chronic Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Because the excitable properties of neurons in the neocortex depend on the characteristics of voltage-gated Na(+) channels, factors which regulate those characteristics can fundamentally modify the dynamics of cortical circuits. Here, we report on a novel neuromodulatory mechanism that links the availability of Na(+) channels to metabolism of polyamines (PAs) in the cerebral cortex. Using single channel and whole-cell recordings, we found that products of PA metabolism, the ubiquitous aliphatic polycations spermine and spermidine, are endogenous blockers of Na(+) channels in layer 5 pyramidal cells. Because the blockade is activity-dependent, it is particularly effective against Na(+) channels which fail to inactivate rapidly and thus underlie the persistent Na(+) current. At the level of the local cortical circuit, pharmacological depletion of PAs led to increased spontaneous spiking and periods of hypersynchronous discharge. Our data suggest that changes in PA levels, whether associated with normal brain states or pathological conditions, profoundly modify Na(+) channel availability and thereby shape the integrative behavior of single neurons and neocortical circuits.
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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.