Mechanisms of orexin 2 receptor-mediated depolarization in the rat paraventricular nucleus of the hypothalamus

Yu Wen E. Dai, Yen Hsien Lee, Tzu Ling Li, Ling Ling Hwang

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Abstract

The paraventricular nucleus of the hypothalamus (PVN) contains dense orexin 2 (OX2) receptor. We examined the mechanisms of OX2 receptor-mediated excitation on electrophysiologically identified type I (putative magnocellular), low-threshold spikes (LTS)-expressing type II (putative preautonomic), and non-LTS type II (putative parvocellular neuroendocrine) neurons. In the presence of tetrodotoxin, an OX2 receptor agonist, ALOXB (30–1000 nM) depolarized 56% of type I, and 73–75% of type II neurons. In type I neurons, ALOXB-induced inward current displayed increased-conductance current-voltage (I–V) relationship and reversed polarity at −27.5 ± 4.8 mV. A Na+-Ca2+ exchanger (NCX) inhibitor, KBR-7943, attenuated ALOXB responses in the majority of type I neurons, while no attenuation was observed in nearly all type II neurons. Type II neurons exhibited three types of I–V relationships in response to ALOXB, characterized by decreased, increased, and unchanged conductance, respectively. The reversal potential of the decreased-conductance responses was near the equilibrium potential of K+ (Ek+) and became more positive in a high-K+ solution, suggesting that K+ conductance blockade is involved. In a low-Na+ solution, non-reversed I–V curves of increased-conductance responses became decreased-conductance responses and reversed polarity near Ek+, suggesting the involvement of both K+ conductance and non-selective cation conductance (NSCC). Approximately 35% of LTS-expressing type II neurons were vasopressin-immunoreactive and 71% of them responded to ALOXB. In conclusion, orexins may activate OX2 receptor on PVN neurons and cause depolarization by promoting NCX and/or NSCC in magnocellular neurons, and by decreasing K+ conductance and/or increasing NSCC in parvocellular neurons. Furthermore, the majority of vasopressinergic preautonomic neurons are under OX2 receptor regulation.

Original languageEnglish
Article number172802
JournalEuropean Journal of Pharmacology
Volume869
DOIs
Publication statusPublished - Feb 15 2020

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Keywords

  • Autonomic neuroscience
  • Ion channel
  • Neuronal excitability
  • Rostral ventrolateral medulla
  • Sympathetic
  • Voltage clamp

ASJC Scopus subject areas

  • Pharmacology

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