Hypercapnia elicits changes in diaphragm neuromotor control and respiratory timing parameters in awake rats

The diaphragm muscle (DIAm) is the primary inspiratory muscle in mammals. At baseline, expiration is passive; however, with increased CO 2 expiration becomes active, involving the inhibition of postinspiratory DIAm activity. The neuromotor control of the DIAm involves both the recruitment and frequency coding of DIAm motor units (MU’s) and it is not clear which aspect plays a greater role with exposure to hypercapnia. The activity of DIAm MU’s can be split into three phases: recruitment, sustained activity, and derecruitment. The goal of the present study was to evaluate the effects of hypercapnia on the neuromotor control of the DIAm in awake Sprague-Dawley rats. We hypothesized that hypercapnia would lead to increased respiratory drive as estimated by the root-mean-square (RMS) EMG amplitude at the end of the recruitment phase. Accordingly, we implanted chronic fine-wire EMG electrodes into the mid-costal region of the right side of the DIAm in 10 (5 female, 5 male) anesthetized rats. Three days after recovery from surgery, we recorded DIAm EMG in lightly restrained awake rats during normocapnia and hypercapnia (7% CO 2 , 21% O 2 , balance N 2 ). We estimated the duration of motor unit recruitment, sustained activity, and derecruitment by assessing the stationarity of DIAm EMG activity and used these durations to determine the RMS EMG amplitude at the completion of recruitment, at the peak, and immediately prior to derecruitment (normalized to the average peak RMS EMG amplitude during normocapnia within each animal). We found that the RMS EMG amplitude at the completion of recruitment was increased from ~75% to 85% with hypercapnia. Peak RMS EMG amplitude during hypercapnia increased from 100% to ~120%, while the amplitude at the onset of derecruitment increased from ~50% to 95%. These data suggest that ~70% of the total RMS EMG peak amplitude can be attributed primarily to motor unit recruitment, while the remaining ~30% can be attributed to frequency modulation during hypercapnia. Importantly the onset-to-offset amplitude difference was ~25% during normocapnia and ~15% during hypercapnia, suggesting that DIAm MU’s were derecruited at higher discharge rates with hypercapnia, likely due to inhibition. We also found that compared to normocapnia, respiratory rate increased from ~85 breaths/min to 125 breaths/min while the burst duration decreased from ~600 ms to ~400 ms during hypercapnia. The duty cycle was maintained around 80% for both, however the duty cycle of the sustained activity duration (i.e. the period during which MU’s are remaining activated) decreased from ~56% to ~28%. Taken together, our data suggest that hypercapnia in awake rats results in an increase in the number of motor units recruited and their discharge rates as well as changes in the phases of DIAm MU activity indicative of active expiration. Funded by NIH HL-146114. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.