Orexin A activates hypoglossal motoneurons and enhances genioglossus muscle activity in rats. (September 2014)

• Record Type: Journal Article
• Authors: Zhang, G H; Liu, Z L; Zhang, B J; Geng, W Y; Song, N N; Zhou, W; Cao, Y X; Li, S Q; Huang, Z L; Shen, L L
• Is Part Of: British journal of pharmacology. Volume 171:Number 18(2014:Sep.)
• Page Start: 4233
• Page End: 4246
• Publication Date: 2014-09
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12784
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12784-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>Orexins have been demonstrated to play important roles in many physiological processes. However, it is not known how orexin A affects the activity of the hypoglossal motoneuron (HMN) and genioglossus (GG) muscle.</p> </sec> <sec id="bph12784-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>GG muscle electromyograms (GG‐EMG) were recorded in anaesthetized adult rats after orexin A or orexin receptor antagonists were applied to the hypoglossal nucleus, and in adult rats in which orexin neurons were lesioned with the neurotoxin orexin‐saporin (orexin‐SAP). HMN membrane potential and firing were recorded from neonatal rat brain slices using whole‐cell patch clamp after an infusion of orexin A or orexin receptor antagonists.</p> </sec> <sec id="bph12784-sec-0003" sec-type="section"> <title>Key Results</title> <p>Unilateral micro‐injection of orexin A (50, 100 or 200 μM) into the hypoglossal nucleus significantly enhanced ipsilateral GG activity in adult rats. Orexin A (4, 20, 100 or 500 nM) depolarized the resting membrane potential and increased the firing rate of HMNs in a dose‐dependent manner in the medullary slices of neonatal rats. Both SB 334867, a specific OX<sub>1</sub> receptor antagonist and TCS OX2 29, a specific OX<sub>2</sub> receptor antagonist not only blocked the depolarized membrane potential and the increased firing rate of HMNs by orexin A in the neonatal model but also attenuated GG‐EMG in the adult model. A significant decrease in GG‐EMG was observed in adult orexin neuron‐lesioned rats compared with sham animals.</p> </sec> <sec id="bph12784-sec-0004" sec-type="section"> <title>Conclusion and Implications</title> <p>Orexin A activates OX<sub>1</sub> and OX<sub>2</sub> receptors within the hypoglossal motor pool and promotes GG activity, indicating that orexin A is involved in controlling respiratory motor activity.</p> </sec> </abstract>