Modulation of Hypoglossal Motoneurons by Nitric Oxide

<p>Obstructive sleep apnea (OSA)- the occurrence of repetitive episodes of airway obstruction during sleep- is considered a major health problem affecting up to 9% of adults in the United States (Parish & Somers, 2004). The hypoglossal motor nucleus (HMN) controls genioglossus muscle tone and is critically important for maintaining airway patency; loss of excitatory input to the HMN during sleep results in disfacilitation of hypoglossal motoneurons, increased airway resistance and contributes to the development of OSA (Horner R. L., 2007). However, a fundamental question of sleep medicine that remains unresolved is what mechanisms help maintain airway patency during sleep? A potential source of sleep-activated compensatory drive is nitric oxide released from cholinergic terminals in the HMN (Pose et al. 2005; Vincent & Kimura, 1992). Here we show that NO functions as an excitatory transmitter in the HMN by a cGMP-dependent inhibition of a background TASK-like conductance and an S-nitrosylation-dependent activation of the instantaneous but not the time-dependent component of the hyperpolarization-activated current (Ih) generated by hyperpolarization-activated cyclic nucleotide gated (HCN) channels. These results suggest that sleep-induced nitrergic innervation of the HMN helps compensate for respiratory motoneuron disfacilitation and disruption of NO/cGMP signaling may contribute to the etiology of OSA. Although a causal link between disruption of NO/cGMP signaling and occurrence of OSA has yet to be established, it is well known that patients with metabolic syndrome have high levels of uric acid- a potent NO scavenger- and, perhaps consequently, are at much higher risk of developing OSA (Mota, 2010).</p>

Name thesis:degree_name

Master of Science

Discipline thesis:degree_discipline

Physiology and Neurobiology

Year dc:date.available

2011

Author dc:creator

• Benoit, Justin Philip

Contributors dc:contributor

• Anastasios Tzingounis; John Morris
• Daniel Mulkey

• motoneurons
• HCN channels
• TASK channels

Repository record dc:identifier

https://digitalcommons.lib.uconn.edu/gs_theses/68

OAI identifier oai:identifier

oai:digitalcommons.lib.uconn.edu:gs_theses-1070