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Mechanisms of orexin 2 receptor-mediated depolarization in the rat paraventricular nucleus of the hypothalamus.
Eur J Pharmacol 2019; :172802EJ

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.

Authors+Show Affiliations

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 110, Taiwan. Electronic address: emily@tmu.edu.tw.Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Taiwan. Electronic address: edward0730@gmail.com.Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 110, Taiwan. Electronic address: electrotmu@gmail.com.Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 110, Taiwan; Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 110, Taiwan. Electronic address: llhwang@tmu.edu.tw.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31738930

Citation

Dai, Yu-Wen E., et al. "Mechanisms of Orexin 2 Receptor-mediated Depolarization in the Rat Paraventricular Nucleus of the Hypothalamus." European Journal of Pharmacology, 2019, p. 172802.
Dai YE, Lee YH, Li TL, et al. Mechanisms of orexin 2 receptor-mediated depolarization in the rat paraventricular nucleus of the hypothalamus. Eur J Pharmacol. 2019.
Dai, Y. E., Lee, Y. H., Li, T. L., & Hwang, L. L. (2019). Mechanisms of orexin 2 receptor-mediated depolarization in the rat paraventricular nucleus of the hypothalamus. European Journal of Pharmacology, p. 172802. doi:10.1016/j.ejphar.2019.172802.
Dai YE, et al. Mechanisms of Orexin 2 Receptor-mediated Depolarization in the Rat Paraventricular Nucleus of the Hypothalamus. Eur J Pharmacol. 2019 Nov 16;172802. PubMed PMID: 31738930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of orexin 2 receptor-mediated depolarization in the rat paraventricular nucleus of the hypothalamus. AU - Dai,Yu-Wen E, AU - Lee,Yen-Hsien, AU - Li,Tzu-Ling, AU - Hwang,Ling-Ling, Y1 - 2019/11/16/ PY - 2019/07/07/received PY - 2019/11/12/revised PY - 2019/11/14/accepted PY - 2019/11/19/pubmed PY - 2019/11/19/medline PY - 2019/11/19/entrez KW - Autonomic neuroscience KW - Ion channel KW - Neuronal excitability KW - Rostral ventrolateral medulla KW - Sympathetic KW - Voltage clamp SP - 172802 EP - 172802 JF - European journal of pharmacology JO - Eur. J. Pharmacol. N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/31738930/Mechanisms_of_orexin_2_receptor-mediated_depolarization_in_the_rat_paraventricular_nucleus_of_the_hypothalamus L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(19)30754-X DB - PRIME DP - Unbound Medicine ER -