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Front. Neurol. | doi: 10.3389/fneur.2019.00155

Ketone bodies inhibit the opening of acid-sensing ion channels (ASICs) in rat hippocampal excitatory neurons in vitro

 Fei Zhu1, Lan Q. Xu1, Shan Wei1,  Chen A. Guo1 and Qun Wang1*
  • 1Beijing Tiantan Hospital, Capital Medical University, China

Objectives: Despite the long-term efficacy of antiepileptic drug treatments, frequent attacks of drug-resistant epilepsy necessitate the development of new antiepileptic drug therapy targets. The ketogenic diet is a high-fat, low-carbohydrate diet that has been shown to be effective in treating drug-resistant epilepsy, although the mechanism is yet unclear. In the ketogenic diet, excess fat is metabolized into ketone bodies (including acetoacetic acid, β-hydroxybutyric acid, and acetone). The present study explored the effect of ketone bodies on acid-sensing ion channels and provided a theoretical basis for the study of new targets of antiepileptic drugs based on” ketone body-acid sensing ion channels.” Methods: In this study, rat primary cultured hippocampal neurons were used. The effects of acetoacetic acid, β-hydroxybutyric acid, and acetone on the open state of acid-sensing ion channels of hippocampal neurons were investigated by the patch-clamp technique. Results: At pH 6.0, the addition of acetoacetic acid, β-hydroxybutyric acid, and acetone in the extracellular solution markedly weakened the currents of acid-sensing ion channels. The three ketone bodies significantly inhibited the opening of the acid-sensing ion channels on the surface of the hippocampal neurons, and 92%, 47%, and 77%, respectively. Conclusions: Ketone bodies significantly inhibit the opening of acid-sensing ion channels. However, a new target for antiepileptic drugs on acid-sensing ion channels is yet to be investigated.

Keywords: Ketone body, Ketogenic Diet, Acid-sensing ion channels, patch clamp, Neuron

Received: 14 Aug 2018; Accepted: 07 Feb 2019.

Edited by:

Xiangping Chu, University of Missouri–Kansas City, United States

Reviewed by:

Qianfa Long, Independent researcher
Giovanni Assenza, Campus Bio-Medico University, Italy  

Copyright: © 2019 Zhu, Xu, Wei, Guo and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Qun Wang, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, qwang64@163.com