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).
","abstract_html":"<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>","abstract_has_math":false,"creators":["Benoit, Justin Philip"],"institution":null,"degree_name":"Master of Science","degree_level":null,"degree_discipline":"Physiology and Neurobiology","degree_department":null,"school":null,"contributors":["Anastasios Tzingounis; John Morris","Daniel Mulkey"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-02T07:00:00Z","date_published":"2011-05-02T07:00:00Z","updated_at":"2026-07-24T06:31:35Z","subjects":["motoneurons","HCN channels","TASK channels"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.lib.uconn.edu/gs_theses/68","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Anastasios Tzingounis; John Morris","Daniel Mulkey"]},{"key":"dc:creator","label":"Author","values":["Benoit, Justin Philip"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2011-05-02T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology and Neurobiology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["motoneurons","HCN channels","TASK channels"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.lib.uconn.edu/gs_theses/68"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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).
"]},{"key":"dc:title","label":"Title","values":["Modulation of Hypoglossal Motoneurons by Nitric Oxide"]}]}],"canonical_facts":{"dc:contributor":["Anastasios Tzingounis; John Morris","Daniel Mulkey"],"dc:creator":["Benoit, Justin Philip"],"dc:date.available":["2011-05-02T07:00:00Z"],"dc:description.abstract":["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).
"],"dc:identifier":["https://digitalcommons.lib.uconn.edu/gs_theses/68"],"dc:subject":["motoneurons","HCN channels","TASK channels"],"dc:title":["Modulation of Hypoglossal Motoneurons by Nitric Oxide"],"thesis:degree_discipline":["Physiology and Neurobiology"],"thesis:degree_name":["Master of Science"]},"updated_at":"2026-07-24T06:31:35Z"}