Changes in preBötzinger Complex neuron discharge associated with changes in PCO2 in decerebrate rabbits

Abstract

Background: Maskrey and Nicol reported a strong increase in minute ventilation with increase in PCO2 (J Physiol 1980, 301: 49-58). We investigated a) whether there was a ceiling to this effect at high CO2 levels and b) whether the change in ventilation was associated with specific changes in respiratory neurons in the preBötzinger complex (preBC). Methods: The study was approved by the local Animal Care Committee and conformed to NIH standards. Adult New Zealand White rabbits (3-4 kg) were anesthetized, tracheotomized, ventilated, decerebrated and vagotomized. Phrenic nerve activity was recorded from the C5 rootlet, time averaged and used to calculate inspiratory (TI) and expiratory durations (TE) and peak phrenic activity (PPA). PPA was normalized to the value at PCO2 50mmHg. Individual neurons were recorded in the functionally identified preBC using multichannel electrodes at increasing CO2 levels. Statistical analysis used the Wilcoxon signed-rank test to determine changes in respiratory parameters between CO2 levels and Friedman RM-ANOVA to determine changes in neuronal discharge frequency (Fn). A generalized linear mixed model was used to determine associations between CO2-dependent changes in TI, TE, PPA, and changes in Fn for different neuron types. p<0.05 indicated a significant difference. Results: In 34 animals, the increase in minute ventilation with increasing PCO2 was due mostly to the change in PPA. The increase in respiratory rate was due mostly to a decrease in TE. There was little increase in respiratory output at PCO2 > 50 mmHg. In 209 neurons, increasing PCO2 increased Fn in inspiratory augmenting (I aug, n= 70, p<0.0001 for CO2 30 vs 40 and 40 vs 50mmHg), I parabolic (I para, n=43, p<0.0001 for CO2 40 vs 50 mmHg), pre-inspiratory (pre-I, n=35, p<0.01 for CO2 30 vs 40 mmHg), and expiratory decrementing (E dec, n=44, p<0.01 for CO2 40 vs 50 mmHg) neurons, but not in I dec (n=8) and non-respiratory modulated (NRM, n=9) neurons. The strongest correlation was found between the changes in phase timing and PPA and Fn in I aug and pre-I neurons. Conclusion: We found a ceiling effect to the increase in respiratory output at PCO2 levels > 50 mmHg. Inspiratory preBC neuron subtypes were more affected by the changes in PCO2. NIH R01HL159546. 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.