Suppression of genioglossus muscle tone and activity during reflex hypercapnic stimulation by GABA(A) mechanisms at the hypoglossal motor nucleus in vivo.
The genioglossus muscle is involved in the maintenance of an open airway for effective breathing. Inhibitory neurotransmitters may be responsible for the major suppression of hypoglossal motor output to genioglossus muscle that occurs in certain behaviours such as rapid-eye-movement sleep. There is evidence for GABA(A) receptor-mediated inhibition of hypoglossal motoneurons in vitro. However, comparable studies have not been performed in vivo and the interactions of such mechanisms with integrative reflex respiratory control have also not been determined. Urethane-anaesthetised, tracheotomized and vagotomized rats were studied whilst diaphragm and genioglossus muscle activities, blood pressure and the electroencephalogram were recorded. Microdialysis probes were implanted into the hypoglossal motor nucleus, with sites verified by histology. Genioglossus responses to microdialysis perfusion of muscimol (GABA(A) agonist: 0, 0.1, 1 and 10 microM in artificial cerebrospinal fluid) were recorded at inspired CO(2)s of 0, 5 and 7.5% in six rats. Responses to bicuculline (GABA(A) antagonist, 0, 1, 10, 100 and 1000 microM) were also studied in six rats with and without CO(2) stimulation. Genioglossus activity decreased with muscimol (P<0.0001), with major suppression at 1 and 10 microM during air breathing (decreases=70.2% and 92.8%, P<0.005). Genioglossus activity increased with CO(2) (P=0.003), but genioglossus activation with 5 and 7.5% CO(2) were almost abolished with 10-microM muscimol. Responses were specific to genioglossus muscle as there were no changes in diaphragm, respiratory rate or blood pressure with muscimol (P>0.144). Antagonism of GABA(A) receptors increased genioglossus activity (P<0.001). These results show that GABA(A) receptor stimulation at the hypoglossal motor nucleus suppresses both genioglossus muscle tone and activity in the presence of reflex stimulation produced by hypercapnia. Recruitment of such mechanisms may contribute to the major suppression of genioglossus activity observed with and without CO(2) stimulation in behaviours such as rapid-eye-movement sleep.
Liu
X
X
Department of Medicine, University of Toronto, Toronto, M5S 1A8, Canada.
Sood
S
S
Liu
H
H
Nolan
P
P
Morrison
J L
JL
Horner
R L
RL
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003964:Diaphragm / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006935:Hypercapnia; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D012018:Reflex / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects / Q000502:physiology*; D014140:Tracheotomy; D014628:Vagotomy
D018755:GABA Agonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D001640:Bicuculline