title: Post-hypoxic recovery of respiratory rhythm generation is gender dependent.
abstract: The preBötzinger complex (preBötC) is a critical neuronal network for the generation of breathing. Lesioning the preBötC abolishes respiration, while when isolated in vitro, the preBötC continues to generate respiratory rhythmic activity. Although several factors influence rhythmogenesis from this network, little is known about how gender may affect preBötC function. This study examines the influence of gender on respiratory activity and in vitro rhythmogenesis from the preBötC. 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 preBötC 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 (KATP) 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 preBötC. 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).
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, United States of America. alfredo.garcia@seattlechildrens.org
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Garcia
authors.forename: Naama
authors.initials: N
authors.lastname: Rotem-Kohavi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Doi
authors.forename: Jan-Marino
authors.initials: JM
authors.lastname: Ramirez
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005260:Female; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D054086:KATP Channels / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010507:Periodicity; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012119:Respiration; D012727:Sex Characteristics; D013569:Synapses / Q000187:drug effects / Q000473:pathology
chemical_list: D054086:KATP Channels; D026902:Potassium Channel Blockers