Cellular mechanisms of orexin actions on paraventricular nucleus neurones in rat hypothalamus

J Physiol. 2002 Dec 15;545(3):855-67. doi: 10.1113/jphysiol.2002.030049.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / pharmacology*
  • Electric Conductivity
  • Electrophysiology
  • Glutamic Acid / physiology
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Neurons / drug effects*
  • Neurons / physiology
  • Neuropeptides / pharmacology*
  • Orexins
  • Osmolar Concentration
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / physiology
  • Patch-Clamp Techniques
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Glutamic Acid