Ketone Body ß-hydroxybutyrate Prevents Seizures by Activating M-Channels
Abstract number :
3.051
Submission category :
1. Basic Mechanisms / 1D. Mechanisms of Therapeutic Interventions
Year :
2018
Submission ID :
502371
Source :
www.aesnet.org
Presentation date :
12/3/2018 1:55:12 PM
Published date :
Nov 5, 2018, 18:00 PM
Authors :
Rian Manville, University of California - Irvine and Geoffrey W. Abbott, University of California - Irvine
Rationale: Ketogenic diets are effective therapies for refractory epilepsy, yet the underlying mechanisms are incompletely understood. Methods: Electrostatic surface potential mapping (ESP), in-silico docking, cellular electrophysiology and pentylenetetrazol (PTZ) seizure assays. Results: BHB directly activates KCNQ2/3 channels, via a highly conserved S5 tryptophan. BHB was also acutely effective as an anticonvulsant in the pentylenetetrazol (PTZ) seizure assay in mice. Conclusions: These data uncover a novel, unexpected molecular basis for anticonvulsant effects of the major ketone body induced by ketosis. Funding: US National Institutes of Health (GM115189 to GWA)