ArticlePloS one2012
Dampening of hyperexcitability in CA1 pyramidal neurons by polyunsaturated fatty acids acting on voltage-gated ion channels.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 26 citations in OpenAlex.
- Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors.The Journal of general physiology · 2018Article
- Atom-by-atom tuning of the electrostatic potassium-channel modulator dehydroabietic acid.The Journal of general physiology · 2018Article
- Non-ketogenic combination of nutritional strategies provides robust protection against seizures.Scientific reports · 2017Article
- Metabolic Dysfunction Underlying Autism Spectrum Disorder and Potential Treatment Approaches.Frontiers in molecular neuroscience · 2017Review
- In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on KFrontiers in physiology · 2016Review
- Synergistic effect of docosahexaenoic acid on anticonvulsant activity of valproic acid and lamotrigine in animal seizure models.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Resin-acid derivatives as potent electrostatic openers of voltage-gated K channels and suppressors of neuronal excitability.Scientific reports · 2015Article
- Ligand-dependent opening of the multiple AMPA receptor conductance states: a concerted model.PloS one · 2015Article
- Drug-induced ion channel opening tuned by the voltage sensor charge profile.The Journal of general physiology · 2014Article
- Hepatic Acyl CoA Oxidase1 Inhibition Modifies Brain Lipids and Electrical Properties of Dentate Gyrus.Basic and clinical neuroscienceArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A ketogenic diet is an alternative treatment of epilepsy in infants. The diet, rich in fat and low in carbohydrates, elevates the level of polyunsaturated fatty acids (PUFAs) in plasma. These substances have therefore been suggested to contribute to the anticonvulsive effect of the diet. PUFAs modulate the properties of a range of ion channels, including K and Na channels, and it has been hypothesized that these changes may be part of a mechanistic explanation of the ketogenic diet. Using computational modelling, we here study how experimentally observed PUFA-induced changes of ion channel activity affect neuronal excitability in CA1, in particular responses to synaptic input of high synchronicity. The PUFA effects were studied in two pathological models of cellular hyperexcitability associated with epileptogenesis. We found that experimentally derived PUFA modulation of the A-type K (K(A)) channel, but not the delayed-rectifier K channel, restored healthy excitability by selectively reducing the response to inputs of high synchronicity. We also found that PUFA modulation of the transient Na channel was effective in this respect if the channel's steady-state inactivation was selectively affected. Furthermore, PUFA-induced hyperpolarization of the resting membrane potential was an effective approach to prevent hyperexcitability. When the combined effect of PUFA on the K(A) channel, the Na channel, and the resting membrane potential, was simulated, a lower concentration of PUFA was needed to restore healthy excitability. We therefore propose that one explanation of the beneficial effect of PUFAs lies in its simultaneous action on a range of ion-channel targets. Furthermore, this work suggests that a pharmacological cocktail acting on the voltage dependence of the Na-channel inactivation, the voltage dependences of K(A) channels, and the resting potential can be an effective treatment of epilepsy.
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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.