title: Cellular mechanisms of orexin actions on paraventricular nucleus neurones in rat hypothalamus.
abstract: Using whole-cell patch clamp techniques we have examined the cellular mechanisms underlying the effects of orexin A (OX-A) on electrophysiologically identified magnocellular and parvocellular neurones in the rat hypothalamic paraventricular nucleus (PVN). The majority of magnocellular neurones (67 %) showed concentration-dependent, reversible depolarizations in response to OX-A. These effects were abolished in tetrodotoxin (TTX), suggesting them to be indirect effects on this population of neurones. OX-A also caused increases in excitatory postsynaptic current (EPSC) frequency and amplitude in magnocellular neurones. The former effects were again blocked in TTX while increases in mini-EPSC amplitude remained. Depolarizing effects of OX-A on magnocellular neurones were also found to be abolished by kynurenic acid, supporting the conclusion that these effects were the result of activation of a glutamate interneurone. Parvocellular neurones (73 % of those tested) also showed concentration-dependent, reversible depolarizations in response to OX-A. In contrast to magnocellular neurones, these effects were maintained in TTX, indicating direct effects of OX-A on this population of neurones. Voltage clamp analysis using slow voltage ramps demonstrated that OX-A enhanced a non-selective cationic conductance with a reversal potential of -40 mV in parvocellular neurones, effects which probably explain the depolarizing effects of this peptide in this subpopulation of PVN neurones. These studies have identified separate cellular mechanisms through which OX-A influences the excitability of magnocellular and parvocellular PVN neurones.
authors.affiliation: Department of Physiology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Follwell
authors.forename: Alastair V
authors.initials: AV
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D018698:Glutamic Acid / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D009994:Osmolar Concentration; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D018698:Glutamic Acid