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Scientific article
Open access
English

Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons

Published inPloS one, vol. 6, no. 2, e16672
Publication date2011
Abstract

We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA) of hypocretin/orexin (hcrt/orx) neurons was changed to an inhibition following sleep deprivation (SD). Here we describe that in control condition (CC), i.e. following 2 hours of natural sleep in the morning, the α(2)-adrenergic receptor (α(2)-AR) agonist, clonidine, had no effect on hcrt/orx neurons, whereas following 2 hours of SD (SDC), it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK) channels. Since concentrations of clonidine up to a thousand times (100 µM) higher than those effective in SDC (100 nM), were completely ineffective in CC, a change in the availability of G-proteins is unlikely to explain the difference between the two conditions. To test whether the absence of effect of clonidine in CC could be due to a down-regulation of GIRK channels, we applied baclofen, a GABA(B) agonist known to also activate GIRK channels, and found that it hyperpolarized hcrt/orx neurons in that condition. Moreover, baclofen occluded the response to clonidine in SDC, indicating that absence of effect of clonidine in CC could not be attributed to down-regulation of GIRK channels. We finally tested whether α(2)-ARs were still available at the membrane in CC and found that clonidine could reduce calcium currents, indicating that α(2)-ARs associated with calcium channels remain available in that condition. Taken together, these results suggest that a pool of α(2)-ARs associated with GIRK channels is normally down-regulated (or desensitized) in hcrt/orx neurons to only become available for their inhibition following sleep deprivation.

Keywords
  • Adrenergic alpha-2 Receptor Agonists/pharmacology
  • Animals
  • Brain/pathology
  • Calcium/metabolism
  • Clonidine/pharmacology
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolism
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Membrane Potentials/drug effects
  • Neurons/drug effects/metabolism/pathology
  • Neuropeptides/metabolism
  • Norepinephrine/metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-2/metabolism
  • Sleep Deprivation/metabolism/pathology
Citation (ISO format)
USCHAKOV, Aaron et al. Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons. In: PloS one, 2011, vol. 6, n° 2, p. e16672. doi: 10.1371/journal.pone.0016672
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1932-6203
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334downloads

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