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

Jones, Barbara E
Published in PLOS ONE. 2011, vol. 6, no. 2, p. e16672
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/pharmacologyAnimalsBrain/pathologyCalcium/metabolismClonidine/pharmacologyG Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolismIntracellular Signaling Peptides and Proteins/metabolismMembrane Potentials/drug effectsNeurons/drug effects/metabolism/pathologyNeuropeptides/metabolismNorepinephrine/metabolismRatsRats, Sprague-DawleyReceptors, Adrenergic, alpha-2/metabolismSleep Deprivation/metabolism/pathology
PMID: 21347440
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Research groups Mécanismes impliqués dans la régulation des états de veille et de sommeil (213)
Culture Primaire de myoblastes humains (208)
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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. https://archive-ouverte.unige.ch/unige:25150

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Deposited on : 2013-01-08

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