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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).
