期刊
JOURNAL OF NEUROPHYSIOLOGY
卷 116, 期 5, 页码 2420-2430出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00327.2016
关键词
4-CIN; FAD autofluorescence; extracellular potassium; sodium and calcium concentrations; lactate shuttle; monocarboxylate transporter
资金
- European Union Grant FP7 Desire [602531-1]
- Deutsche Forschungsgemeinschaft (DFG) [He1128/18-1]
- DFG [Ko3814/1-1]
- EXC Neurocure [EXC 257]
Astrocyte-derived lactate supports pathologically enhanced neuronal metabolism, but its role under physiological conditions is still a matter of debate. Here, we determined the contribution of astrocytic neuronal lactate shuttle for maintenance of ion homeostasis and energy metabolism. We tested for the effects of alpha-cyano-4-hydroxycinnamic acid (4-CIN), which could interfere with energy metabolism by blocking monocarboxylate-transporter 2 ( MCT2)-mediated neuronal lactate uptake, on evoked potentials, stimulus-induced changes in K+, Na-+,Na- Ca2+, and oxygen concentrations as well as on changes in flavin adenine dinucleotide ( FAD) autofluorescence in the hippocampal area CA3. MCT2 blockade by 4-CIN reduced synaptically evoked but not antidromic population spikes. This effect was dependent on the activation of K-ATP channels indicating reduced neuronal ATP synthesis. By contrast, lactate receptor activation by 3,5-dihydroxybenzoic acid ( 3,5-DHBA) resulted in increased antidromic and orthodromic population spikes suggesting that 4-CIN effects are not mediated by lactate accumulation and subsequent activation of lactate receptors. Recovery kinetics of all ion transients were prolonged and baseline K+ concentration became elevated by blockade of lactate uptake. Lactate contributed to oxidative metabolism as both baseline respiration and stimulus-induced changes in PO2 were decreased, while FAD fluorescence increased likely due to a reduced conversion of FAD into FADH(2). These data suggest that lactate shuttle contributes to regulation of ion homeostatsis and synaptic signaling even in the presence of ample glucose.
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