sleep-deprivation regulates α-2 adrenergic responses of rat hypocretinorexin neurons缺乏睡眠调节α-2肾上腺素的老鼠hypocretinorexin神经元的反应.pdf

Sleep-Deprivation Regulates a-2 Adrenergic Responses of Rat Hypocretin/Orexin Neurons 1. 1. 1 1 1 Aaron Uschakov , Jeremy Grivel , Vesna Cvetkovic-Lopes , Laurence Bayer , Laurent Bernheim , 2 ¨ 1 1 Barbara E. Jones , Michel Muhlethaler , Mauro Serafin * ´ ´ ` 1 Departement de Neurosciences fondamentales, Centre Medical Universitaire, Geneve, Switzerland, 2 Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada 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 a -adrenergic receptor (a -AR) agonist, clonidine, had no effect on 2 2 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 mM) 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 GABAB agonist known to also activate GIRK ch