title: Orexin-A depolarizes nucleus tractus solitarius neurons through effects on nonselective cationic and K+ conductances.
abstract: The nucleus tractus solitarius (NTS) plays central roles in a number of autonomic functions including cardiovascular control. Orexin (ORX)-A is a 33-amino-acid peptide implicated in the central regulation of energy metabolism, sleep, and the cardiovascular system. Studies demonstrate the presence of ORX-immunoreactive axons and both OX(1)R (orexin receptor) and OX(2)R mRNA within NTS. In this study, whole cell patch-clamp recordings were obtained from NTS neurons in rat medullary slices. Current-clamp studies showed that bath application of various concentrations of ORX-A depolarized 90.7% (78 of 86) of neurons tested while the remaining cells were either unaffected or showed small hyperpolarizations in response to peptide administration. Depolarizing effects were maintained in the presence of 5 microM TTX, and were concentration dependent. Using voltage-clamp techniques, we also identified modulatory actions of ORX-A on specific ion channels. Our results demonstrate that not only does ORX-A inhibit a specific potassium conductance (the sustained K(+) current) in NTS neurons, but it also activates a nonselective cationic conductance (NSCC). These data suggest that ORX-A effects on central cardiovascular control may result from direct actions on NTS neurons and also highlight the ability of this peptide to influence neuronal excitability as a consequence of concurrent modulation of multiple ion channels.
authors.affiliation: Department of Physiology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Alastair V
authors.initials: AV
authors.lastname: Ferguson
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D002412:Cations; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D015221:Potassium Channels; D011188:Potassium