Post-Hypoxic Recovery of Respiratory Rhythm Generation Is Gender Dependent

The preBotzinger complex (preBotC) is a critical neuronal network for the generation of breathing. Lesioning the preBotC abolishes respiration, while when isolated in vitro, the preBotC continues to generate respiratory rhythmic activity. Although several factors influence rhythmogenesis from this network, little is known about how gender may affect preBotC function. This study examines the influence of gender on respiratory activity and in vitro rhythmogenesis from the preBotC. Recordings of respiratory activity from neonatal mice (P10-13) show that sustained post-hypoxic depression occurs with greater frequency in males compared to females. Moreover, extracellular population recordings from the preBotC in neonatal brainstem slices (P10-13) reveal that the time to the first inspiratory burst following reoxygenation (TTFB) is significantly delayed in male rhythmogenesis when compared to the female rhythms. Altering activity of ATP sensitive potassium channels (K-ATP) with either the agonist, diazoxide, or the antagonist, tolbutamide, eliminates differences in TTFB. By contrast, glucose supplementation improves post-hypoxic recovery of female but not male rhythmogenesis. We conclude that post-hypoxic recovery of respiration is gender dependent, which is, in part, centrally manifested at the level of the preBotC. Moreover, these findings provide potential insight into the basis of increased male vulnerability in a variety of conditions such as Sudden Infant Death Syndrome (SIDS).