Nicotinic excitation of rat hypoglossal motoneurons.
Hypoglossal motoneurons (HMNs), which innervate the tongue muscles, are involved in several important physiological functions, including the maintenance of upper airway patency. The neural mechanisms that affect HMN excitability are therefore important determinants of effective breathing. Obstructive sleep apnea is a disorder characterized by recurrent collapse of the upper airway that is likely due to decline of pharyngeal motoneuron activity during sleep. Because cholinergic neuronal activity is closely coupled to wake and sleep states, we tested the effects and pharmacology of nicotinic acetylcholine receptor (nAChR) activation on HMNs. We made intracellular recordings from HMNs in medullary slices from neonatal rats and found that local application of the nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium iodide, excited HMNs by a Ca(2+)-sensitive, and TTX-insensitive inward current that was blocked by dihydro-beta-erythroidine (IC(50): 19+/-3 nM), methyllycaconitine (IC(50): 32+/-7 nM), and mecamylamine (IC(50): 88+/-11 nM), but not by alpha-bungarotoxin (10 nM). This is consistent with responses being mediated by postsynaptic nAChRs that do not contain the alpha7 subunit. These results suggest that nAChR activation may contribute to central maintenance of upper airway patency and that the decline in firing rate of cholinergic neurons during sleep could potentially disfacilitate airway dilator muscle activity, contributing to airway obstruction.
Chamberlin
N L
NL
Department of Neurology, Beth Israel Deaconess Medical Center, 77 Ave Louis Pasteur, Boston, MA 02115, USA. nchamber@caregroup.harvard.edu
Bocchiaro
C M
CM
Greene
R W
RW
Feldman
J L
JL
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D018679:Cholinergic Agonists / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives*; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D012890:Sleep / Q000502:physiology*; D020181:Sleep Apnea, Obstructive / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D018679:Cholinergic Agonists; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide; C013411:biocytin; D008239:Lysine