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

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, whic...Continue Reading

  • References
  • Citations55

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations55

Citations

Mentioned in this Paper

KCNJ8 gene
alpha-cyano-4-hydroxycinnamic acid
Neogluconin
Energy Supply
alpha-cyano-4-hydroxycinnamate
Lactate
Extracellular
Toxin
Intracellular Signaling Proteins
Sodium Channel Blockers

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.