ArticleThe Journal of biological chemistry2009
Aminopyridines potentiate synaptic and neuromuscular transmission by targeting the voltage-activated calcium channel beta subunit.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Study on Dalfampridine in the treatment of Multiple Sclerosis Mobility Disability: A meta-analysis.PloS one · 2019Pooled it
- A double-blind, randomized, controlled study of two dose strengths of dalfampridine extended release on walking deficits in ischemic stroke.Restorative neurology and neuroscience · 2020Trial
- Ion channel and receptor-mediated regulation of axonal conduction reliability in sympathetic preganglionic neurons.bioRxiv : the preprint server for biology · 2026Article
- Exploring the use of dalfampridine (4-aminopyridine) for treatment of ataxia in cerebellar stroke.PM & R : the journal of injury, function, and rehabilitation · 2026Article
- Characterizing the Diversity of Layer 2/3 Human Neocortical Neurons in Pediatric Epilepsy.eNeuro · 2025Article
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Sleep Deprivation-Induced Anxiety Alleviated by Oral Administration of 4-Aminopyridine in Male Mice.Brain and behavior · 2025Article
- Article
- Investigating the Safety of Fampridine in Patients with Different Stages of Multiple Sclerosis.International journal of preventive medicine · 2025Article
- Morphological Tracing and Functional Identification of Monosynaptic Connections in the Brain: A Comprehensive Guide.Neuroscience bulletin · 2024Review
- Single shot detection of alterations across multiple ionic currents from assimilation of cell membrane dynamics.Scientific reports · 2024Article
- Simple dynamic cell culture system reduces recording noise in microelectrode array recordings.MRS communications · 2024Article
- Future targets for migraine treatment beyond CGRP.The journal of headache and pain · 2023Review
- 4-Aminopyridine Induces Nerve Growth Factor to Improve Skin Wound Healing and Tissue Regeneration.Biomedicines · 2022Article
- Acute axon damage and demyelination are mitigated by 4-aminopyridine (4-AP) therapy after experimental traumatic brain injury.Acta neuropathologica communications · 2022Article
- Hyperactivation is sufficient to release porcine sperm from immobilized oviduct glycans.Scientific reports · 2022Article
- An Imidazoline 2 Receptor Ligand Relaxes Mouse AortaFrontiers in pharmacology · 2022Article
- Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron-Astrocyte Co-Cultures.International journal of molecular sciences · 2021Article
- Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update.Brain sciences · 2021Review
- Comparison of KHandbook of experimental pharmacology · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Aminopyridines such as 4-aminopyridine (4-AP) are widely used as voltage-activated K(+) (Kv) channel blockers and can improve neuromuscular function in patients with spinal cord injury, myasthenia gravis, or multiple sclerosis. Here, we present novel evidence that 4-AP and several of its analogs directly stimulate high voltage-activated Ca(2+) channels (HVACCs) in acutely dissociated neurons. 4-AP, 4-(aminomethyl)pyridine, 4-(methylamino)pyridine, and 4-di(methylamino)pyridine profoundly increased HVACC, but not T-type, currents in dissociated neurons from the rat dorsal root ganglion, superior cervical ganglion, and hippocampus. The widely used Kv channel blockers, including tetraethylammonium, alpha-dendrotoxin, phrixotoxin-2, and BDS-I, did not mimic or alter the effect of 4-AP on HVACCs. In HEK293 cells expressing various combinations of N-type (Cav2.2) channel subunits, 4-AP potentiated Ca(2+) currents primarily through the intracellular beta(3) subunit. In contrast, 4-AP had no effect on Cav3.2 channels expressed in HEK293 cells. Furthermore, blocking Kv channels did not mimic or change the potentiating effects of 4-AP on neurotransmitter release from sensory and motor nerve terminals. Thus, our findings challenge the conventional view that 4-AP facilitates synaptic and neuromuscular transmission by blocking Kv channels. Aminopyridines can directly target presynaptic HVACCs to potentiate neurotransmitter release independent of Kv channels.
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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.