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


METHODS
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.


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.


CONCLUSIONS
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.
Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai, China; Department of Physiology, Basic Medical College of Zhengzhou University, Zhengzhou, China.
G H
GH
Zhang
Z L
ZL
Liu
B J
BJ
Zhang
W Y
WY
Geng
N N
NN
Song
W
W
Zhou
Y X
YX
Cao
S Q
SQ
Li
Z L
ZL
Huang
L L
LL
Shen
D000818:Animals; D000831:Animals, Newborn; D004576:Electromyography; D007002:Hypoglossal Nerve / Q000502:physiology*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008564:Membrane Potentials; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D064446:Orexin Receptors / Q000502:physiology*; D000068797:Orexins; D017207:Rats, Sprague-Dawley
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins