Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
Details
State: Public
Version: author
Serval ID
serval:BIB_12EB0722775A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
Journal
PLoS One
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
8
Number
8
Pages
e71721
Language
english
Abstract
Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary neurons was monitored by calcium imaging. When applied in conjunction with glucose, lactate induced a decrease in the spontaneous calcium spiking frequency of neurons. The effect was reversible and concentration dependent (IC50 ∼4.2 mM). To test whether lactate effects are dependent on energy metabolism, we applied the closely related substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or 10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi protein-coupled receptor for lactate called HCA1 has been introduced. To test if this receptor is implicated in the observed lactate sensitivity, we incubated cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a specific agonist of the HCA1 receptor, mimicked the action of lactate. This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism, independent from its intracellular metabolism.
Pubmed
Web of science
Open Access
Yes
Create date
20/12/2013 12:39
Last modification date
20/08/2019 13:41