Orexin A activates hypoglossal motoneurons and enhances genioglossus muscle activity in rats

Abstract

Background and Purpose 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. Experimental Approach 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. Key Results 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 OX1 receptor antagonist and TCS OX2 29, a specific OX2 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. Conclusion and Implications Orexin A activates OX1 and OX2 receptors within the hypoglossal motor pool and promotes GG activity, indicating that orexin A is involved in controlling respiratory motor activity.

Early improvement in obstructive sleep apnea and increase in orexin levels after bariatric surgery in adolescents and young adults

“…The fact that 1) orexin neurons are involved in sensing the body's external and internal environments (14-16) , 2) orexin neurons have a role in stimulating upper airway (17) and central respiratory neurons (12) , and 3) our findings showing increased orexin levels after bariatric surgery are all facts that support our speculation that neurophysiologic mechanisms may be responsible for the observed changes in OSA.…”

Orexins increase the firing activity of nigral dopaminergic neurons and participate in motor control in rats

“…Microinjection of SB 334867 or TCS OX2 29 into the hypoglossal nucleus decreases the tonic genioglossus activity, which suggests the involvement of endogenous orexins in the regulation of genioglossus muscle activity in rats (Zhang et al . ). In addition, endogenous orexins also play important roles in food intake (Terrill et al .…”

Signaling mechanism underlying the histamine‐modulated action of hypoglossal motoneurons

“…Techniques used for medullary slice preparations were similar to those described previously for HMNs (Zhang et al . ). Briefly, the pups were anesthetized by chloral hydrate (5%), decapitated, and their brainstems were rapidly removed.…”

“…Our previous studies sustained the above hypothesis and revealed that, orexin A released from the hypothalamic orexinergic neurons increases GG activity via activation of orexin receptors in medullary HMNs (Zhang et al . ). Likewise, histaminergic drive, an important component of the arousal system (Huang et al .…”