The Lactate Receptor HCAR1 Modulates Neuronal Network Activity through the Activation of G
Action Potentials
Animals
Calcium Signaling
/ drug effects
Cells, Cultured
Cerebral Cortex
/ cytology
Cyclic AMP
/ physiology
Excitatory Postsynaptic Potentials
/ drug effects
Female
Heterotrimeric GTP-Binding Proteins
/ physiology
Lactates
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Miniature Postsynaptic Potentials
/ drug effects
Nerve Tissue Proteins
/ agonists
Neurons
/ drug effects
Primary Cell Culture
Receptors, G-Protein-Coupled
/ agonists
Second Messenger Systems
/ drug effects
GPR81
HCAR1
intracellular pathway
lactate
neurons
spontaneous activity
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
05 06 2019
05 06 2019
Historique:
received:
10
08
2018
revised:
19
03
2019
accepted:
22
03
2019
pubmed:
31
3
2019
medline:
23
6
2020
entrez:
31
3
2019
Statut:
ppublish
Résumé
The discovery of a G-protein-coupled receptor for lactate named hydroxycarboxylic acid receptor 1 (HCAR1) in neurons has pointed to additional nonmetabolic effects of lactate for regulating neuronal network activity. In this study, we characterized the intracellular pathways engaged by HCAR1 activation, using mouse primary cortical neurons from wild-type (WT) and HCAR1 knock-out (KO) mice from both sexes. Using whole-cell patch clamp, we found that the activation of HCAR1 with 3-chloro-5-hydroxybenzoic acid (3Cl-HBA) decreased miniature EPSC frequency, increased paired-pulse ratio, decreased firing frequency, and modulated membrane intrinsic properties. Using fast calcium imaging, we show that HCAR1 agonists 3,5-dihydroxybenzoic acid, 3Cl-HBA, and lactate decreased by 40% spontaneous calcium spiking activity of primary cortical neurons from WT but not from HCAR1 KO mice. Notably, in neurons lacking HCAR1, the basal activity was increased compared with WT. HCAR1 mediates its effect in neurons through a G
Identifiants
pubmed: 30926749
pii: JNEUROSCI.2092-18.2019
doi: 10.1523/JNEUROSCI.2092-18.2019
pmc: PMC6554634
doi:
Substances chimiques
Hcar1 protein, mouse
0
Lactates
0
Nerve Tissue Proteins
0
Receptors, G-Protein-Coupled
0
Cyclic AMP
E0399OZS9N
Heterotrimeric GTP-Binding Proteins
EC 3.6.5.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4422-4433Informations de copyright
Copyright © 2019 the authors.
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