After-discharge in the upper airway muscle genioglossus following brief hypoxia

Abstract

Study Objectives Genioglossus after-discharge is thought to protect against pharyngeal collapse by minimising periods of low upper airway muscle activity. How genioglossus after-discharge occurs and which single motor units (SMUs) are responsible for the phenomenon are unknown. The aim of this study was to investigate genioglossal after-discharge. Methods During wakefulness, after-discharge was elicited 8-12 times in healthy individuals with brief isocapnic hypoxia (45-60s of 10%O2 in N2) terminated by a single breath of 100% O2. Genioglossus SMUs were designated as firing solely, or at increased rate, during inspiration (Inspiratory phasic [IP] and inspiratory tonic [IT] respectively); solely, or at increased rate, during expiration (Expiratory phasic [EP] or expiratory tonic [ET] respectively) or firing constantly without respiratory modulation (Tonic). SMUs were quantified at baseline, the end of hypoxia, the hyperoxic breath and the following 8 normoxic breaths. Results 210 SMU’s were identified in 17 participants. Genioglossus muscle activity was elevated above baseline for 7 breaths after hyperoxia (p<0.001), indicating a strong after-discharge effect. After-discharge occurred due to persistent firing of IP and IT units that were recruited during hypoxia, with minimal changes in ET, EP or Tonic SMUs. The firing frequency of units that were already active changed minimally during hypoxia or the afterdischarge period (P>0.05). Conclusion That genioglossal after-discharge is almost entirely due to persistent firing of previously silent inspiratory SMUs provides insight into the mechanisms responsible for the phenomenon and supports the hypothesis that the inspiratory and expiratory/tonic motor units within the muscle have idiosyncratic functions.

The influence of alcohol on genioglossus single motor units in men and women during wakefulness

“…Data from the placebo session in these participants have been reported in a recent publication (Avraam et al, 2021) (Nicholas et al, 2010;Vecchio et al, 2010;Wilkinson et al, 2008Wilkinson et al, , 2010Woods et al, 2015). Transition of units between IP and IT units is common (Nicholas et al, 2010;Wilkinson et al, 2010), and likewise conversion of EP/ET to TT and vice versa have been observed (Nicholas et al, 2010).…”

“…Participants were not informed as to which experimental session was which, but most were able to correctly identify the alcohol from placebo session. Data from the placebo session in these participants have been reported in a recent publication (Avraam et al., 2021). Participants were between 19 and 35 years old, had regular sleep patterns (waking regularly between 07.00 and 10.00 h) with good self‐reported sleep quality and did not smoke or take medications (except the oral contraceptive pill).…”

“…After this practice trial and at least 3 min of recovery, resting breathing was recorded for 5 min. Subsequently, 8–12 brief periods of isocapnic hypoxia were delivered to assess afterdischarge as per our prior publication (Avraam et al., 2021 ). Briefly, each hypoxia trial consisted of a further minute of baseline recording (Baseline) before 45–60 s of hypoxia (Hypoxia – 10% O 2 in N 2 ), which was introduced without warning.…”

“…The aim of this study was therefore to assess the influence of alcohol on genioglossus MUs in awake humans. A secondary aim was to investigate the effect of alcohol on the genioglossus afterdischarge (the slow decline in activity after sudden removal of an excitatory stimulus), which we have recently shown to occur predominantly due to IP and IT units (Avraam, Dawson et al., 2021 ).…”

Upper airway muscles: influence on obstructive sleep apnoea pathophysiology and pharmacological and technical treatment options

“…The administration of a selective agonist for the new excitatory receptor increased the genioglossus tonic electromyographic activity greater than six-fold compared with baseline. There are several steps to be taken in order to apply DREADDs and chemogenetic techniques to humans with OSA; however, these procedures represent to date the most targeted attempt to treat OSA with medications and hold great potential for the future of the field [89].…”