title: Opposing muscarinic and nicotinic modulation of hypoglossal motor output to genioglossus muscle in rats in vivo.
abstract: The genioglossus (GG) muscle of the tongue, innervated by the hypoglossal motor nucleus (HMN), helps maintain an open airway for effective breathing. In vitro studies in neonatal rodents have separately characterized muscarinic and nicotinic receptor influences at the HMN but the net effects of combined nicotinic and muscarinic receptor activation and increased endogenous acetylcholine have not been determined in adult animals in vivo. Urethane-anaesthetized, tracheotomized and vagotomised rats were studied. Microdialysis perfusion of acetylcholine into the HMN significantly decreased respiratory-related GG activity (28.5 +/- 11.0% at a threshold dose of 0.1 mm). Application of the cholinergic agonists carbachol and muscarine have similar suppression effects (GG activity was decreased 11.8 +/- 4.3 and 20.5 +/- 5.8%, respectively, at 0.01 microm). Eserine, an acetylcholinesterase inhibitor, also decreased the amplitude of respiratory-related GG activity (36.4 +/- 11.3% at 1.0 microm) indicating that endogenous acetylcholine modulates GG activity. Although these results showed that suppression of GG activity predominates during cholinergic stimulation at the HMN, application of the nicotinic receptor agonist dimethyl-4-phenylpiperazinium iodide significantly increased tonic and respiratory-related GG activity (156 +/- 33% for respiratory activity at 1.0 mm) showing that excitatory responses are also present. Consistent with this, 100 microm carbachol decreased GG activity by 44.2 +/- 7.5% of control, with atropine (10 microm) reducing this suppression to 13.8 +/- 4.0% (P < 0.001). However, the nicotinic receptor antagonist dihydro-beta-erythroidine (100 microm) increased the carbachol-mediated suppression to 69.5 +/- 5.9% (P = 0.011), consistent with a role for nicotinic receptors in limiting the overall suppression of GG activity during cholinergic stimulation. Application of eserine to increase endogenous acetylcholine also showed that inhibitory muscarinic and excitatory nicotinic receptors together determine the net level of GG activity during cholinergic stimulation at the HMN. The results suggest that acetylcholine has mixed effects at the HMN with muscarinic-mediated GG suppression masking nicotinic excitation.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada, M5S 1A8.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sood
authors.forename: Hattie
authors.initials: H
authors.lastname: Liu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Horner
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D007002:Hypoglossal Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D017551:Microdialysis; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D014059:Tongue / Q000294:innervation*
chemical_list: D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D002245:Carbon Dioxide; D004246:Dimethylphenylpiperazinium Iodide; D008464:Mecamylamine; D001285:Atropine; D002217:Carbachol