Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro
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...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-03-01
|
Series: | Frontiers in Neurology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2019.00155/full |
id |
doaj-9244929cbb4c40f595f25213a8cad902 |
---|---|
record_format |
Article |
spelling |
doaj-9244929cbb4c40f595f25213a8cad9022020-11-24T22:09:25ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-03-011010.3389/fneur.2019.00155419269Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitroFei Zhu0Fei Zhu1Fei Zhu2Fei Zhu3Wei Shan4Wei Shan5Wei Shan6Wei Shan7Qinlan Xu8Qinlan Xu9Qinlan Xu10Anchen Guo11Anchen Guo12Jianping Wu13Jianping Wu14Jianping Wu15Qun Wang16Qun Wang17Qun Wang18Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaNational Center for Clinical Medicine of Neurological Diseases, Beijing, ChinaBeijing Institute for Brain Disorders, Beijing, ChinaAdvanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaNational Center for Clinical Medicine of Neurological Diseases, Beijing, ChinaBeijing Institute for Brain Disorders, Beijing, ChinaAdvanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaNational Center for Clinical Medicine of Neurological Diseases, Beijing, ChinaBeijing Institute for Brain Disorders, Beijing, ChinaNational Center for Clinical Medicine of Neurological Diseases, Beijing, ChinaBeijing Institute for Brain Disorders, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaNational Center for Clinical Medicine of Neurological Diseases, Beijing, ChinaAdvanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, ChinaDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaNational Center for Clinical Medicine of Neurological Diseases, Beijing, ChinaBeijing Institute for Brain Disorders, Beijing, ChinaObjectives: 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.https://www.frontiersin.org/article/10.3389/fneur.2019.00155/fullketone bodyketogenic dietacid-sensing ion channelspatch clampneuron |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fei Zhu Fei Zhu Fei Zhu Fei Zhu Wei Shan Wei Shan Wei Shan Wei Shan Qinlan Xu Qinlan Xu Qinlan Xu Anchen Guo Anchen Guo Jianping Wu Jianping Wu Jianping Wu Qun Wang Qun Wang Qun Wang |
spellingShingle |
Fei Zhu Fei Zhu Fei Zhu Fei Zhu Wei Shan Wei Shan Wei Shan Wei Shan Qinlan Xu Qinlan Xu Qinlan Xu Anchen Guo Anchen Guo Jianping Wu Jianping Wu Jianping Wu Qun Wang Qun Wang Qun Wang Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro Frontiers in Neurology ketone body ketogenic diet acid-sensing ion channels patch clamp neuron |
author_facet |
Fei Zhu Fei Zhu Fei Zhu Fei Zhu Wei Shan Wei Shan Wei Shan Wei Shan Qinlan Xu Qinlan Xu Qinlan Xu Anchen Guo Anchen Guo Jianping Wu Jianping Wu Jianping Wu Qun Wang Qun Wang Qun Wang |
author_sort |
Fei Zhu |
title |
Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro |
title_short |
Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro |
title_full |
Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro |
title_fullStr |
Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro |
title_full_unstemmed |
Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro |
title_sort |
ketone bodies inhibit the opening of acid-sensing ion channels (asics) in rat hippocampal excitatory neurons in vitro |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2019-03-01 |
description |
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. |
topic |
ketone body ketogenic diet acid-sensing ion channels patch clamp neuron |
url |
https://www.frontiersin.org/article/10.3389/fneur.2019.00155/full |
work_keys_str_mv |
AT feizhu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT feizhu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT feizhu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT feizhu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT weishan ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT weishan ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT weishan ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT weishan ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT qinlanxu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT qinlanxu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT qinlanxu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT anchenguo ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT anchenguo ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT jianpingwu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT jianpingwu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT jianpingwu ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT qunwang ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT qunwang ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro AT qunwang ketonebodiesinhibittheopeningofacidsensingionchannelsasicsinrathippocampalexcitatoryneuronsinvitro |
_version_ |
1725811962801029120 |