Ketogenic Diet Metabolites Reduce Firing in Central Neurons by Opening KATPChannels
Open Access
- 4 April 2007
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 27 (14), 3618-3625
- https://doi.org/10.1523/jneurosci.0132-07.2007
Abstract
A low-carbohydrate ketogenic diet remains one of the most effective (but mysterious) treatments for severe pharmacoresistant epilepsy. We have tested for an acute effect of physiological ketone bodies on neuronal firing rates and excitability, to discover possible therapeutic mechanisms of the ketogenic diet. Physiological concentrations of ketone bodies (β-hydroxybutyrate or acetoacetate) reduced the spontaneous firing rate of neurons in slices from rat or mouse substantia nigra pars reticulata. This region is thought to act as a “seizure gate,” controlling seizure generalization. Consistent with an anticonvulsant role, the ketone body effect is larger for cells that fire more rapidly. The effect of ketone bodies was abolished by eliminating the metabolically sensitive KATPchannels pharmacologically or by gene knock-out. We propose that ketone bodies or glycolytic restriction treat epilepsy by augmenting a natural activity-limiting function served by KATPchannels in neurons.Keywords
This publication has 64 references indexed in Scilit:
- Update on the Role of Substantia Nigra Pars Reticulata in the Regulation of SeizuresEpilepsy Currents, 2006
- Glut‐1 deficiency syndrome: Clinical, genetic, and therapeutic aspectsAnnals of Neurology, 2004
- Dynamic activation of KATP channels in rhythmically active neuronsThe Journal of Physiology, 2001
- Protective Role of ATP-Sensitive Potassium Channels in Hypoxia-Induced Generalized SeizureScience, 2001
- Sulfonylurea and K+-Channel Opener Sensitivity of KATP ChannelsThe Journal of general physiology, 1999
- ATP-sensitive K + channels and insulin secretion: their role in health and diseaseDiabetologia, 1999
- A re‐examination of adult mouse nicotinic acetylcholine receptor channel activation kineticsThe Journal of Physiology, 1999
- PIP 2 and PIP as Determinants for ATP Inhibition of K ATP ChannelsScience, 1998
- The Kinetics, Substrate, and Inhibitor Specificity of the Monocarboxylate (Lactate) Transporter of Rat Liver Cells Determined Using the Fluorescent Intracellular pH Indicator, 2′,7′-Bis(carboxyethyl)-5(6)-carboxyfluoresceinPublished by Elsevier BV ,1996
- Cardiac ATP-sensitive K+ channels. Evidence for preferential regulation by glycolysis.The Journal of general physiology, 1989