help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on August 24, 2006, doi:10.1164/rccm.200605-597OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 11, December 2006, 1264-1273

A more recent version of this article appeared on December 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200605-597OCv1
174/11/1264    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chan, E.
Right arrow Articles by Horner, R. L
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chan, E.
Right arrow Articles by Horner, R. L

Submitted on May 3, 2006
Accepted on August 22, 2006

Endogenous Excitatory Drive Modulating Respiratory Muscle Activity Across Sleep-Wake States

Erin Chan1, Hendrik W Steenland1, Hattie Liu1, and Richard L Horner1*

1 Department of Medicine and Physiology, University of Toronto, Toronto, ON, Canada

* To whom correspondence should be addressed. E-mail: richard.horner{at}utoronto.ca.

Rationale: The concept of a tonic drive activating respiratory muscle in wakefulness but not sleep has been an important and enduring notion in respiratory medicine, not least because it is useful in modelling sleep effects on breathing and understanding the pathogenesis of sleep- related breathing disorders such as obstructive sleep apnea (OSA). However, a neurotransmitter substrate mediating respiratory muscle activation across sleep-wake states has not been identified. Objectives: To determine if {alpha}1 receptor antagonism at the hypoglossal motor nucleus (HMN) will decrease genioglossus activity consistent with a role for an endogenous noradrenergic drive contributing to genioglossus activation across sleep-wake states. We also determined if {alpha}1 receptor stimulation could counteract reduced endogenous noradrenergic drive and increase sleeping GG activity. Methods: Thirty-five rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states, and genioglossus and diaphragm electrodes for respiratory muscle recordings. Microdialysis probes were inserted into the HMN. Measurements and Main Results: Microdialysis perfusion of the {alpha}1 receptor antagonist terazosin into the HMN significantly decreased genioglossus activity in wakefulness and non-rapid eye movement (non-REM) sleep but not REM sleep. The {alpha}1 receptor agonist phenylephrine increased genioglossus activity in wakefulness and sleep but periods of motor inactivity still persisted in REM; there was no potentiating effect of combined {alpha}1 and 5-HT2 receptor stimulation. Conclusions: Identification of an endogenous noradrenergic drive contributing to GG activation in wakefulness and non-REM sleep, but not REM, is important given the prevalence and clinical significance of sleep-induced hypoventilation and OSA in humans and potential for pharmacological treatment.
Key words: Sleep, Obstructive Sleep Apnea; Hypoglossal Motor Nucleus, Genioglossus Muscle, Noradrenaline




This article has been cited by other articles:


Home page
 J. Neurosci.Home page
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]

Home page
 J. Neurosci.Home page
C. Burgess, D. Lai, J. Siegel, and J. Peever
An Endogenous Glutamatergic Drive onto Somatic Motoneurons Contributes to the Stereotypical Pattern of Muscle Tone across the Sleep-Wake Cycle
J. Neurosci., April 30, 2008; 28(18): 4649 - 4660.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
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]

Home page
 J. Neurosci.Home page
Y. Zhu, P. Fenik, G. Zhan, E. Mazza, M. Kelz, G. Aston-Jones, and S. C. Veasey
Selective Loss of Catecholaminergic Wake Active Neurons in a Murine Sleep Apnea Model
J. Neurosci., September 12, 2007; 27(37): 10060 - 10071.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
S. Sood, X. Liu, H. Liu, and R. L. Horner
Genioglossus muscle activity and serotonergic modulation of hypoglossal motor output in obese Zucker rats
J Appl Physiol, June 1, 2007; 102(6): 2240 - 2250.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. L. Horner and T. D. Bradley
Update in Sleep and Control of Ventilation 2006
Am. J. Respir. Crit. Care Med., March 1, 2007; 175(5): 426 - 431.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2006 American Thoracic Society