Chronic Intermittent Hypoxia Alters Genioglossus Motor Unit Discharge Patterns in the Anaesthetized Rat
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The respiratory control system is subject to diverse and considerable plasticity in health and disease. Intermittent hypoxia elicits expression of intrinsic plasticity within sensory and motor pathways involved in the control of breathing with potentially adaptive and maladaptive consequences for respiratory homeostasis. We and others have shown that chronic intermittent hypoxia (CIH) – a major feature of sleep-disordered breathing – has deleterious effects on rat upper airway dilator muscle contractile function and motor control. In the present study, we sought to test the hypothesis that CIH alters genioglossus (pharyngeal dilator) motor unit properties during basal breathing and obstructive airway events. Adult male Wistar rats were exposed to 20 cycles of normoxia and hypoxia (5% O2 at nadir; SaO2 ∼ 80%) per hour, 8 h a day for 7 days (CIH, N = 5). The sham group (N = 5) were subject to alternating cycles of air under identical experimental conditions in parallel. Following gas treatments, rats were anaesthetized with an i.p injection of urethane (1.5 g/kg; 20% w/v). Fine concentric needle electrodes were inserted into the genioglossus and the costal diaphragm. Genioglossus motor unit potentials, together with arterial blood pressure, tracheal pressure and arterial O2 saturation were recorded during quiet basal breathing and nasal airway occlusion. During basal breathing, the amplitude of genioglossus motor units was significantly different in sham vs. CIH-treated rats (313 ± 32 μV vs. 430 ± 46 μV; mean ± SEM, Student’s t test, p = 0.0415). The most common instantaneous firing frequency of individual units determined from auto correlograms was also significantly different in the two groups (53 ± 6 Hz vs. 37 ± 3 Hz; sham vs. CIH p = 0.0318). In addition, the amplitude of motor units recruited during airway obstruction was significantly decreased in CIH-treated rats (939 ± 102 μV vs. 619 ± 75 μV; sham vs. CIH p = 0.0267). Our results indicate that CIH causes remodelling in the central respiratory motor network with potentially maladaptive consequences for the physiological control of upper airway patency. We conclude that CIH could serve to exacerbate and perpetuate obstructive events in patients with sleep-disordered breathing.
KeywordsAnaesthetized rat Plasticity Chronic intermittent hypoxia Upper airway Genioglossus Single motor unit Recruitment Motor control Oxidative injury.
Supported by the Health Research Board, Ireland (RP/2007/29). DE is enrolled in the School of Medicine and Medical Science Translational Medicine PhD training programme.
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