Jun 18, 2010

ATP-sensitive potassium channel-mediated lactate effect on orexin neurons: implications for brain energetics during arousal

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Matthew P Parsons, Michiru Hirasawa


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, whic...Continue Reading

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Mentioned in this Paper

KCNJ8 gene
alpha-cyano-4-hydroxycinnamic acid
Energy Supply
Intracellular Signaling Proteins
Sodium Channel Blockers

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