ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
ATP-sensitive potassium channel-mediated lactate effect on orexin neurons: implications for brain energetics during arousal.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.Molecular psychiatry · 2013Pooled it
- Brain glucose uptake is associated with endogenous glucose production in obese patients before and after bariatric surgery and predicts metabolic outcome at follow-up.Diabetes, obesity & metabolism · 2019Trial
- The right temperature at the right time: A framework for understanding thermoregulatory pathophysiology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Written in the Stars: Astrocyte Biology From Evolution to Disease.Acta physiologica (Oxford, England) · 2026Review
- Article
- The Lactate Nexus: A Molecular Bridge Linking Physical Activity, Sleep, and Cognitive Enhancement.Biomedicines · 2026Review
- Metabolic interactions in the brain: the crucial roles of neurons, astrocytes, and microglia in health and disease.Frontiers in neuroscience · 2026Review
- Gestational High-Fat Diet Drives Premature Differentiation of Orexigenic Neurons and Reactivity of Astrocytes in the Fetal Rat Lateral Hypothalamus.Brain sciences · 2025Article
- Lac-Phe induces hypophagia by inhibiting AgRP neurons in mice.Nature metabolism · 2025Article
- ATP-sensitive potassium channels alter glycolytic flux to modulate cortical activity and sleep.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lactate-induced metabolic signaling is the potential mechanism for reshaping the brain function - role of physical exercise.Frontiers in endocrinology · 2025Review
- Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms.Journal of neuroinflammation · 2024Review
- Distinct Neuromodulatory Effects of Endogenous Orexin and Dynorphin Corelease on Projection-Defined Ventral Tegmental Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture.Nature communications · 2024Article
- Astrocyte-Neuronal Communication and Its Role in Stroke.Neurochemical research · 2023Review
- Lactate: A Theranostic Biomarker for Metabolic Psychiatry?Antioxidants (Basel, Switzerland) · 2023Review
- Peripheral and Central Impact of Methionine Source and Level on Growth Performance, Circulating Methionine Levels and Metabolism in Broiler Chickens.Animals : an open access journal from MDPI · 2023Article
- Serotonergic neurons control cortical neuronal intracellular energy dynamics by modulating astrocyte-neuron lactate shuttle.iScience · 2023Article
- Role of astrocytes in sleep deprivation: accomplices, resisters, or bystanders?Frontiers in cellular neuroscience · 2023Review
- Activation of lactate receptor HCAR1 down-modulates neuronal activity in rodent and human brain tissue.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
Abstract
Active neurons have a high demand for energy substrate, which is thought to be mainly supplied as lactate by astrocytes. Heavy lactate dependence of neuronal activity suggests that there may be a mechanism that detects and controls lactate levels and/or gates brain activation accordingly. Here, we demonstrate that orexin neurons can behave as such lactate sensors. Using acute brain slice preparations and patch-clamp techniques, we show that the monocarboxylate transporter blocker alpha-cyano-4-hydroxycinnamate (4-CIN) inhibits the spontaneous activity of orexin neurons despite the presence of extracellular glucose. Furthermore, fluoroacetate, a glial toxin, inhibits orexin neurons in the presence of glucose but not lactate. Thus, orexin neurons specifically use astrocyte-derived lactate. The effect of lactate on firing activity is concentration dependent, an essential characteristic of lactate sensors. Furthermore, lactate disinhibits and sensitizes these neurons for subsequent excitation. 4-CIN has no effect on the activity of some arcuate neurons, indicating that lactate dependency is not universal. Orexin neurons show an indirect concentration-dependent sensitivity to glucose below 1 mm, responding by hyperpolarization, which is mediated by ATP-sensitive potassium channels composed of Kir6.1 and SUR1 subunits. In conclusion, our study suggests that lactate is a critical energy substrate and a regulator of the orexin system. Together with the known effects of orexins in inducing arousal, food intake, and hepatic glucose production, as well as lactate release from astrocytes in response to neuronal activity, our study suggests that orexin neurons play an integral part in balancing brain activity and energy supply.
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