| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Departments of Medicine and Physiology, University of Toronto, Toronto, M5S 1A8, Canada
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 µM). Eserine, an acetylcholinesterase inhibitor, also decreased the amplitude of respiratory-related GG activity (36.4 ± 11.3% at 1.0 µM) 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 µM carbachol decreased GG activity by 44.2 ± 7.5% of control, with atropine (10 µM) reducing this suppression to 13.8 ± 4.0% (P < 0.001). However, the nicotinic receptor antagonist dihydro-ß-erythroidine (100 µM) 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.
(Received 7 February 2005;
accepted after revision 6 April 2005;
first published online 7 April 2005)
Corresponding author R. L. Horner: Room 6368 Medical Sciences Building, 1 Kings College Circle, Toronto, Ontario, Canada, M5S 1A8. Email: richard.horner{at}utoronto.ca
This article has been cited by other articles:
|
|
 |
|
  H. W. Steenland, H. Liu, and R. L. Horner Endogenous Glutamatergic Control of Rhythmically Active Mammalian Respiratory Motoneurons In Vivo J. Neurosci., July 2, 2008; 28(27): 6826 - 6835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Brooks and J. H. Peever Glycinergic and GABAA-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia J. Neurosci., April 2, 2008; 28(14): 3535 - 3545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Moraes, D. Poyares, L. Sukys-Claudino, C. Guilleminault, and S. Tufik Donepezil Improves Obstructive Sleep Apnea in Alzheimer Disease: A Double-Blind, Placebo-Controlled Study Chest, March 1, 2008; 133(3): 677 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Buyse and the participants of working group 2 Treatment effects of sleep apnoea: where are we now? Eur. Respir. Rev., December 1, 2007; 16(106): 146 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Peters, M. Conrad, C. Hubold, U. Schweiger, B. Fischer, and H. L. Fehm The principle of homeostasis in the hypothalamus-pituitary-adrenal system: new insight from positive feedback Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R83 - R98. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Chan, H. W. Steenland, H. Liu, and R. L. Horner Endogenous Excitatory Drive Modulating Respiratory Muscle Activity across Sleep-Wake States Am. J. Respir. Crit. Care Med., December 1, 2006; 174(11): 1264 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sood, E. Raddatz, X. Liu, H. Liu, and R. L. Horner Inhibition of serotonergic medullary raphe obscurus neurons suppresses genioglossus and diaphragm activities in anesthetized but not conscious rats J Appl Physiol, June 1, 2006; 100(6): 1807 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. A. Aoki, H. Liu, G. P. Downey, J. Mitchell, and R. L. Horner Cyclic Nucleotides Modulate Genioglossus and Hypoglossal Responses to Excitatory Inputs in Rats Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 555 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Ryan and T. D. Bradley Pathogenesis of obstructive sleep apnea J Appl Physiol, December 1, 2005; 99(6): 2440 - 2450. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
